MXPA01002978A - Genes of the 1-desoxy-d-xylulose biosynthetic pathway - Google Patents

Abstract

The invention relates to the 1-desoxy- D-xylulose- 5-phosphate reductoisomerase gene, the 1-desoxy- D-xylulose- 5-phosphate- synthase gene and the gcpE gene of the 1-desoxy- D-xylulose biosynthetic pathway and to their use for transforming vectors, host organisms and plants and for determining substances that inhibit this biosynthetic pathway.

Description

GENES OF THE BIOSYNTHESIS PATH OF 1-DESOXY-D-XILULOSE The present invention relates to DNA sequences which, when incorporated into the genome of viruses, eukaryotes and prokaryotes, modify the isoprenoid biosynthesis; and a genetic engineering process for the production of these transgenic, eukaryotic and prokaryotic viruses. The invention also relates to a process for the identification of substances having herbicidal, antimicrobial, antiparasitic, antiviral, fungicidal, bactericidal action in plants; and antimicrobial, antiparasitic, antifungal, antibacterial and antiviral action in humans and animals. The trajectory of biosynthesis for the formation of isoprenoids is already known, through the classical path of acetate / metavalonate and a trajectory of biosynthesis independent of mevalonate, alternative, the trajectory of deoxy-D-xylulose phosphate. (Rohmer, M., Knani, M. and Simonin, P., Sutter, B. and Sahm, H (1993): Biochem. J. 295: 517-524). However, it is unknown how and by what trajectories it is possible to effect a change in the isoprenoid concentration in viruses, eukaryotes and prokaryotes, by means of the pathway of deoxy-D-xylulose phosphate. Figure 1 shows this biosynthesis trajectory. Accordingly, DNA sequences encoding the 5-phosphate synthase of 1-deoxy-D-xylulase (DOXP-) are provided. synthase), the 5-phosphate reductoisomerase of 1-deoxy-D-xylulose (DOXP reductoisomerase) or the gcpE protein. All three genes and enzymes are involved in isoprenoid biosynthesis. The gcpE protein has a kinase function and catalyzes the phosphorylation of a sugar or a phosphorous sugar or a precursor of isoprenoid biosynthesis, in particular the phosphorylation of 2-C-methyl-D-erythritol, 2-C-methyl-phosphate. D-erythritol, in particular 2-C-methyl-D-erythritol 4-phosphate, 2-C-methyl-D-erythrose, 2-C-methyl-D-erythrose phosphate, in particular 4-phosphate 2 -C-methyl-D-erythrose. In the precursor of isoprenoid synthesis, the gcpE protein in particular catalyzes the phosphorylation of the following substances:. CH2 (OH) -C (CH3) = C (OH) -CH2-O-PO (OH) 2, CH2 (OH) -C (CH3) = C (OH) -CH2-OH, CH2 (OH) -CH (CH3) -CO-CH2-O-PO (OH) 2, CH2 (OH) -CH (CH3) -CO-CH2OH CH2 = C (CH3) -CO-CH2-O-PO (OH) 2l CH2 = C (CH3) -CO-CH2-OH, CH2 = C (CH3) -CH (OH) -CH2-O-PO (OH) 2, CH2 = C (CH3) -CH (OH) -CH2-OH, CH2 (CH2) OH) -C (= CH2) -C (OH) -CH2-O-PO (OH) 2, CH2 (OH) -C (= CH2) -C (OH) -CH2-OH, CHO-CH (CH3) -CH (OH) -CH2-O-PO- (OH) 2, CHO-CH (CH3) -CH (OH) -CH2-OH, CH2 (OH) -C (OH) (CH3) -CH = CH- O-PO (OH) 2, CH 2 (OH) -C (OH) (CH 3) -CH = CH-OH, CH (OH) = C (CH3) -CH (OH) -CH2-O-PO (OH) 2, CH (OH) = C (CH3) -CH (OH) -CH2-OH, (CH3) 2HC-CO -CH2-O-PO (OH) 2, (CH3) 2HC-CO-CH2-OH, (CH3) 2HC-CH (OH) -CH2-O-PO (OH) 2, (CH3) 2HC-CH (OH ) -CH2-OH. DOXP-synthase catalyzes the condensation of pyruvate and glyceraldehyde 3-phosphate, to produce 5-phosphate of 1-deoxy-D-xylulose, and DOXP-reductoisomerase catalyzes the conversion of 5-phosphate from 1-deoxy-D-xylulose to 4-phosphate 2-C-methyl-D-erythritol (see figure 1). The invention relates to the following DNA sequences: DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO: 2, or an analog or derivative of the polypeptide according to SEQ ID NO: 2, wherein one or more amino acids have been omitted, added or replaced by other amino acids; where the enzymatic action of the polypeptide is retained; and said sequences originate from parasites; where the sequence variations that occur within the framework of natural strain variability are included. DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO. 4 or an analog or derivative of the polypeptide according to SEQ ID NO: 4; in which one or more amino acids have been omitted, added or replaced by other amino acids; where the enzymatic action of the polypeptide is retained; and said sequences originate from parasites; where sequence variations that occur within the framework of natural strain variability are included; and DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO. 6, or an analog or derivative of the polypeptide according to SEQ ID NO. 6, in which one or more amino acids have been omitted, added or replaced by other amino acids; where the catalytic function of the polypeptide is retained. 5-Phosphate and DOXP-reductoisomerase catalyze the conversion of 5-phosphate from 1-deoxy-D-xylulose to 4-phosphate from 2-C-methyl-D-erythritol (see Figure 1). The invention relates to the following DNA sequences: DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO. 2, or an analog or derivative of the polypeptide according to SEQ ID NO: 2, wherein one or more amino acids have been omitted, added or replaced by other amino acids; DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO: 4 or an analog or derivative of the polypeptide according to SEQ ID NO 4; where one or more amino acids have been omitted, added or replaced by other amino acids; Y DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO. 6, or an analog or derivative of the polypeptide according to SEQ ID. DO NOT. 6, where one or more amino acids have been omitted, added or replaced by other amino acids. The genes and their gene products (polypeptides) are shown with their primary structures, and have been assigned in the following manner: SEQ ID NO: 1: 5-phosphate 5-phosphate reductoisomerase gene of 1-deoxy-D-xylulose; SE.Q ID NO. 2: 5-phosphate reductoisomerase of 1-deoxy-D-xylulose. SEQ ID NO: 3: 5-phosphate synthase gene of 1-deoxy-D-xylulose.

SEQ ID NO. 4: 5-phosphate synthase of 1-deoxy-D-xylulose. SEQ ID NO. 5: gcpE gene. SEQ ID NO. 6: gcpE proteins. All DNA sequences originate from Plasmodium falciparum. In addition to the DNA sequences indicated in the sequence listings, suitable sequences are also those which, as a result of the degeneracy of the genetic code, have another DNA sequence, but encode the same peptide or an analog or derivative of the polypeptide, in the that one or more amino acids have been omitted, added or replaced by other amino acids. The sequences according to the invention are suitable for the expression of genes in viruses, eukaryotes and prokaryotes, which are responsible for isoprenoid biosynthesis, in the path of 1-deoxy-D-xylulose. According to the invention, eukaryotes or eukaryotic cells include animal cells, plant cells, algae, yeast, fungi; while prokaryotes or prokaryotic cells include bacteria, archaebacteria and eubacteria. When a DNA sequence is incorporated into a genome in which the DNA sequence indicated above is located, the expression of the genes described above in viruses, eukaryotes and prokaryotes is enabled. The viruses, eukaryotes and prokaryotes transformed according to the invention are cultured in a manner known per se, and the isoprenoid formed during said culture is isolated and optionally purified. Not all isoprenoids need to be isolated, since in some cases, isoprenoids are released directly into the ambient air. The invention further relates to a process for the production of transgenic, eukaryotic and prokaryotic viruses in order to modify the content of the sopranoid; process comprising the following steps: a) .- Production of a DNA sequence with the following subsequences: i) promoter, which is active in viruses, eukaryotes and prokaryotes, and which guarantees the formation of an RNA in the target tissue or the target cells to which it is addressed; ii) DNA sequence encoding a polypeptide with the amino acid sequence shown in SEQ ID NO: 2, 4 or 6, or an analog or derivative of the polypeptide according to SEQ ID NO: 2, 4 or 6; iii) sequence not translated 5 'and 3', which allows or increases the expression of the genes indicated in viruses, eukaryotes and prokaryotes; b) Transfer and incorporation of the DNA sequence into the genome of viruses, prokaryotic or eukaryotic cells, with or without the use of a vector (for example, plasmid, viral, DNA). Whole intact plants can be regenerated from cells of plants transformed in that way. The protein coding sequences, with the nucleotide sequences SEQ ID NO: 1, SEQ ID NO: 3 AND SEQ ID NO: 5 can be provided with a promoter that guarantees transcription in certain organs or cells; promoter that is coupled in consensual orientation (3 'end of the promoter to the 5' end of the coding sequence), with respect to the sequence encoding the protein to be formed. A termination signal, which determines the termination of the mRNA synthesis, is fixed to the 3 'end of the coding sequence. In order to direct the protein to be expressed, to certain subcellular compartments, such as chloroplasts, amyloplasts, mitochondria, vacuoles, cytosol or intercellular spaces, another sequence encoding a so-called signal sequence or a transit peptide between the promoter and the coding sequence. In some cases it is necessary to insert sequences that encode a signal at the COOH end of the protein. The sequence must be in the same reading frame as the coding sequence of the protein. A large number of cloning vectors are available in order to prepare the introduction of the DNA sequences according to the invention, in higher plants; vectors that contain a signal of replication (reproduction) for E. coli, and a marker that allows the selection of the transformed cells. Depending on the method by which the desired genes are introduced into the plant, additional DNA sequences may be necessary. For example, i use the Ti or Ri plasmid to transform the plant cells, at least one right edge, but frequently the right edge and the left edge of the T-DNA of the Ti and Ri plasmid must be inserted as a flanking region in the genes that are going to be introduced. The use of T-DNA for transforming plant cells has been extensively investigated and described in an inclusive manner in EP 120516; Hoekama, in The Binary Plant Vector System, Offset-drukkerij Kanters B.V. Alblasserdam (1985), chapter V; Fraley and coauthors, Crit. Rev. Plant Sci., 4, 1-46, and An and coauthors (1985), EMBO J., 4, 277-287. Once the introduced DNA has been incorporated into the genome, it is generally stable and is also retained in the descendants of the originally transformed cells. It usually contains a marker selection, which imparts to the transformed plant cells, resistance to a biocide or an antibiotic, such as kanamycin, G 418, bleomycin, hygromycin or phosphinothricin, and others. The particular marker used, thereby, is intended to allow the selection of transformed cells from cells lacking the inserted DNA. Many techniques are available to introduce DNA into a plant. These techniques include the transformation with the help of agrobacteria, for example, Agrobacterium tumefaciens, protoplast fusion, DNA macroinjection, electroporation, as well as a ballistic method and virus infection. Then whole plants of the transformed plant material can be regenerated in a suitable medium, which can contain antibiotics or biocides for selection purposes. No particular requirement is imposed on the plasmids for injection and electroporation. However, if entire plants are to be regenerated from said transformed cells, a selectable marker gene must be present. Transformed cells grow in plants in the conventional manner (McCormick and co-authors, (1986), Plant Cells Report, 5, 81-84). Plants can be grown normally and can be crossed with plants that have the same transformed genome or other genomes. The resulting individuals have the corresponding phenotypic properties. The present invention also provides expression vectors containing one or more of the DNA sequences of according to the invention. Said expression vectors are obtained by providing suitable functional regulation signals in the DNA sequences according to the invention. Said regulatory signals are DNA sequences that are responsible for the expression, for example, promoters, operators, enhancers, ribosomal binding sites, and are recognized by the host organism. Other regulatory signals, which, for example, control the reproduction or recombination of recombinant DNA in the host organism, can also be a constituent part of the expression vector. Also provided by the present invention are host organisms transformed with the DNA sequences or expression vectors according to the invention. The cells and host organisms suitable for expressing the enzymes according to the invention are those which do not comprise intrinsic enzymes with the function of DOXPsintase, DOXP-reductoisomerase or gcpE protein. This is the case of archaebacteria, animals, fungi, slurry molds and some eubactaries. The absence of said intrinsic enzyme activity substantially facilitates the detection and purification of recombinant enzymes. As a consequence, it is also possible, for the first time, to directly measure, in crude extracts from the host cells, the activity; and in particular, the inhibition of the activity of the recombinant enzymes according to the invention, by various chemical and pharmaceutical substances. The enzymes according to the invention are then expressed, advantageously, in eukaryotic cells, if post-translational modification and natural folding of the polypeptide chain is to be obtained. Furthermore, depending on the expression system, it is guaranteed, when expressing genomic DNA sequences, that introns are removed by dividing the DNA and the enzymes are produced in the polypeptide sequences characteristic for the parasites. Using recombinant DNA techniques, the sequences encoding the introns can be deleted, or inserted for experimental purposes, into the DNA sequences to be expressed. The protein of the host cell or the culture supernatant of the host cell can be isolated, using methods known to the person skilled in the art. Reactivation of enzymes in vitro may also be required. In order to facilitate the purification, the enzymes according to the invention or the subsequences of the enzymes, such as fusion proteins, can be expressed with various peptide chains. Oligo-histidine sequences and sequences derived from glutathione-S-transferase, thio-redoxin or peptides that bind to calmodulin, are particularly suitable for that purpose. The enzymes according to the invention, or the subsequences of the enzymes, can be further expressed as fusion proteins, with peptide chains known to those skilled in the art, that the recombinant enzymes are transported to the extracellular medium or to certain compartments of the host cells. Consequently, both the purification and the investigation of the biological activity of the enzymes can be facilitated. When expressing the enzymes according to the invention, it may be convenient to modify individual codons. The proposed replacement of bases in the coding region may also be advisable here if the codons used in the parasites differ from the codon used in the heterologous expression system, in order to guarantee the optimal synthesis of the protein. Additionally, the enzymes according to the invention can be obtained under standard conditions, by in vitro translation, by methods known to the person skilled in the art. Suitable systems for this purpose are rabbit reticulocytes and wheat germ extracts, and bacterial lysates. Transcribed mRNA in vitro can also be transferred to Xenopus oocytes. Oligopeptides and polypeptides, whose sequences are derived from the peptide sequence of the enzymes according to the invention, can be obtained by chemical synthesis. Given the proper selection of the sequences, these peptides have properties that are characteristic of the enzymes according to the invention. These peptides can be produced in large and are particularly suitable for investigating the kinetics of enzymatic activity, the regulation of enzymatic activity, the three-dimensional structure of enzymes, the inhibition of enzymatic activity by various chemical and pharmaceutical substances, and the binding geometry and affinity of binding of various ligands. Preferably DNA is used with the nucleotides of the sequences SEQ ID NO: 1, 3 and 5, for the recombinant production of the enzymes according to the invention. Accordingly, the invention further relates to a process for selecting compounds that inhibit the metabolic pathway of deoxy-D-xylulose phosphate. In accordance with this process, a host organism is provided, which contains a recombinant expression vector, wherein the vector constitutes at least a portion of the oligonucleotide sequence according to SEQ ID NO: 1, SEQ ID NO: 3 or SEQ ID NO: 5, or its variants or its counterparts; as well as a compound that is suspected to have antimicrobial, antiparasitic, antibacterial, antiviral and antifungal action in humans and animals, or an antimicrobial, antiviral, bactericidal, herbicidal or fungicidal activity in plants. The host organism is then contacted with the compound and the activity of the compound is determined. The present invention also provides methods for determining the enzymatic activity of the gcpE protein. That activity can be determined using known methods. It is carried determination by detecting the phosphorylation of a sugar or a phosphorus sugar or a precursor of isoprenbiosynthesis, in particular the phosphorylation of 2-C-methyl-D-erythritol, 2-C-methyl-D-erythritol phosphate , in particular 2-C-methyl-D-erythritol 4-phosphate, 2-C-methyl-D-erythrose, 2-C-methyl-D-erythrose phosphate, in particular 2-C-methyl 4-phosphate -D-eritrosa. The present invention also provides the use of this measurement method to identify substances that inhibit the activity of particular enzymes. The enzymatic activity of DOXP-synthase and DOXP-reductoisomerase can be detected in a single step, determining the conversion of glyceraldehyde 3-phosphate to 4-phosphate of 2-C-methyleritritol. The determination of the activities of DOXP-synthase and DOXP-reductoisomerase proceeds analogously. Also suitable are the fluorimetric methods described by Querol and co-authors, which are also suitable for determining the activity of DOXP-synthase (Querol and co-authors, Abstracts, 4th European Symposium on Plant Isopren, Barcelona, 21-23 April 1999).

LI S T ION D E S EC U S < 110 > Jomaa, Hassan < 120 > Genes of the biosynthesis pathway of 1-deoxy-D-xylulose < 130 > 15696 < 140 > PCT / EP99 < 141 > 1999-09-22 < 150 > DE19923567.8 < 151 > 1999-05-22 < 150 > DE19843279.8 < 151 > 1998-09-22 < 160 > 6 < 170 > Patentln Ver. 2.1 < 210 > 1 < 211 > 1467 < 212 > DNA < 213 > Plasmodium falciparum < 220 > < 221 > CDS < 222 > (1) .. (1467) < 220 > < 221 > gene < 222 > (1) .. (1467) < 220 > < 221 > MRNA < 222 > (1) .. (1467) < 400 > 1 atg aag aaa tat att ata tat ata ttt ttc ttc ate ata ata ata att 48 Met Lys Lys Tyr He Tyr He Tyr Phe Phe Phe He Thr He Thr He 1 5 10 15 aat gat tta gta ata aat aat here tea aaa tgt gtt tec att gaa aga 96 Asn Asp Leu Val He Asn Asn Thr Ser Lys Cys Val Ser He Glu Arg 20 25 30 aga aaa aat aac gca tat ata aat tat ggt ata gga tat aat gga cca 144 Arg Lys Asn Asn Wing Tyr He Asn Tyr Gly He Gly Tyr Asn Gly Pro 35 40 45 gat aat aaa ata ata aag agt aga aga tgt aaa aga ata aag tta tgc 192 Asp Asn Lys He Thr Lys Ser Arg Arg Cys Lys Arg He Lys Leu Cys 50 55 60 aaa aag gat tta ata gat att ggt gca ata aag aaa cca att aat gta 240 Lys Lys Asp Leu He Asp He Gly Wing He Lys Lys Pro He Asn Val 65 70 75 80 gca att ttt gga agt act ggt agt ata ggt acg aat gct tta aat ata 288 Wing He Phe Gly Ser Thr Gly Ser He Gly Thr Asn Ala Leu Asn He 85 90 95 ata agg gag tgt aat aaa att gaa aat gtt ttt aat gtt aaa gca ttg 336 He Arg Glu Cys Asn Lys He Glu Asn Val Phe Asn Val Lys Ala Leu 100 105 110 tat gtg aat aag agt gtg aat gaa tta tat gaa ca gct aga gaa ttt 384 Tyr Val Asn Lys Ser Val Asn Glu Leu Tyr Glu Gln Ala Arg Glu Phe 115 120 125 tta cca gaa tat ttg tgt ata cat gat aaa agt gta tat gaa gaa tta 432 Leu Pro Glu Tyr Leu Cys He His Asp Lys Ser Val Tyr Glu Glu Leu 130 135 140 aaa gaa ctg gta aaa aat ata aaa gat tat aaa ect ata ata ttg tgt 480 Lys Glu Leu Val Lys Asn He Lys Asp Tyr Lys Pro He He Leu Cys 145 150 155 160 ggt gat gaa ggg atg aaa gaa ata tgt agt agt aat agt ata gat aaa 528 Gly Asp Glu Gly Met Lys Glu He Cys Ser Ser Asn Ser He Asp Lys 165 170 175 ata gtt att ggt att gat tet ttt ca gga tta tat tet act atg tat 576 He Val He Gly He Asp Ser Phe Gln Gly Leu Tyr Ser Thr Met Tyr 180 185 190 gca att atg aat aat aaa ata gtt gcg tta gct aat aaa gaa tec att 624 Ala He Met Asn Asn Lys He Val Ala Leu Ala Asn Lys Glu Ser He 195 200 205 gtc tet gct gt ttc ttt tta aag aaa tta tta aat att cat aaa aat 672 Val Ser Wing Gly Phe Phe Leu Lys Lys Leu Leu Asn líe His Lys Asn 210 215 220 gca aag ata ata ect gtt gat tea gaa cat agt gct ata ttt cata tgt 720 Wing Lys He He Pro Val Asp Ser Glu His Ser Wing He Phe Gln Cys 225 230 235 240 tta gat aat aat aag gta tta aaa here aaa tgt tta ca a gac aat ttt 768 Leu Asp Asn Asn Lys Val Leu Lys Thr Lys Cys Leu Gln Asp Asn Phe 245 - 250 255 tet aaa att aac aat ata aat aaa ata ttt tta tgt tea tet gga ggt 816 Ser Lys He Asn Asn He Asn Lys He Phe Leu Cys Ser Ser Gly Gly 260 265 270 cca ttt caat aat tta act atg gac gaa tta aaa aat gta here tea gaa 864 Pro Phe Gln Asn Leu Thr Met Asp Glu Leu Lys Asn Val Thr Ser Glu 275 280 285 aat gct tta aag cat ect aaa tgg aaa atg ggt aag aaa ata act ata 912 Asn Ala Leu Lys His Pro Lys Trp Lys Met Gly Lys Lys He Thr He 290 295 300 gat tet gca act atg atg aat aaa ggt tta gag gtt ata gaa acc cat 960 Asp Be Ala Thr Met Met Asn Lys Gly Leu Glu Val He Glu Thr His 305 310 315 320 ttt tta ttt gat gta gat tat aat gat ata gaa gtt ata gta cat aaa 1008 Phe Leu Phe Asp Val Asp Tyr Asn Asp He Glu Val Ie Val His Lys 325 330 335 gaa tgc att ata cat tet tgt gtt gaa ttt ata gac aaa tea gta ata 1056 Glu Cys He He His Ser Cys Val Glu Phe He Asp Lys Ser Val He 340 345 350 agt caa atg tat tat cca gat atg caa ata ecc ata tta tat tet tta 1104 Ser Gln Met Tyr Tyr Pro Asp Met Gln He Pro He Leu Tyr Ser Leu 355 360 365 here tgg ect gat aga ata aaa here aat tta aaa ect tta gat ttg gct 1152 Thr Trp Pro Asp Arg He Lys Thr Asn Leu Lys Pro Leu Asp Leu Wing 370 375 380 cag gtt tea act ctt here ttt cat aaa ect tet tta gaa cat tcc ccg 1200 Gln Val Ser Thr Leu Thr Phe His Lys Pro Ser Leu Glu His Phe Pro 385 390 395 400 tgt att aaa tta gct tat ca gca ggt ata aaa gga aac ttt tat cca 1248 Cys He Lys Leu Wing Tyr Gln Wing Gly He Lys Gly Asn Phe Tyr Pro 405 410 415 act gta cta aat gcg tea aat gaa ata gct aac aac tta ttt ttg aat 1296 Thr Val Leu Asn Wing Ser Asn Glu He Wing Asn Asn Leu Phe Leu Asn 420 425 430 aat aaa att aaa tat ttt gat att tet ata ata ata teg ca gtt ctt 1344 Asn Lys He Lys Tyr Phe Asp He Ser Ser He He Ser Gln Val Leu 435 440 445 gaa tet ttc aat tet caa aag gtt teg gaa aat agt gaa gat tta atg 1392 Glu Ser Phe Asn Ser Gln Lys Val Ser Glu Asn Ser Glu Asp Leu Met 450 455 460 AAG CAA ATTA CAT CA AT CAT TET TAG GCC Aaa GET Aaa GACT ACC GET ACC 1440 Lys Gln He Leu Gln He His Ser Trp Wing Lys Asp Lys Wing Thr Asp 465 470 475 480 ata tac aac aaa cat aat tet tea tag 1467 He Tyr Asn Lys His Asn Ser Ser 485 < 210 > 2 < 211 > 488 < 212 > PRT < 213 > Plasmodium falciparum < 400 > 2 Met Lys Lys Tyr He Tyr He Tyr Phe Phe Phe He Thr He Thr He 1 5 10 15 Asn Asp Leu Val He Asn Asn Thr Ser Lys Cys Val Ser He Glu Arg 20 25 30 Arg Lys Asn Asn Wing Tyr He Asn Tyr Gly He Gly Tyr Asn Gly Pro 35 40 45 Asp Asn Lys He Thr Lys Ser Arg Arg Cys Lys Arg He Lys Leu Cys 50 55 60 Lys Lys Asp Leu He Asp He Gly Wing He Lys Lys Pro He Asn Val 65 70 75 80 Wing He Phe Gly Ser Thr Gly Ser He Gly Thr Asn Ala Leu Asn He 85 90 95 He Arg Glu Cys Asn Lys He Glu Asn Val Phe Asn Val Lys Ala Leu 100 105 110 Tyr Val Asn Lys Ser Val Asn Glu Leu Tyr Glu Gln Wing Arg Glu Phe 115 120 125 Leu Pro Glu Tyr Leu Cys He His Asp Lys Ser Val Tyr Glu Glu Leu 130 135 140 Lys Glu Leu Val Lys Asn He Lys Asp Tyr Lys Pro He He Leu Cys 145 150 155 160 Gly Asp Glu Gly Met Lys Glu He Cys Ser Ser Asn Ser He Asp Lys 165 170 175 He Val He Gly He Asp Ser Phe Gln Gly Leu Tyr Ser Thr Met Tyr 180 185 '190 Wing He Met Asn Asn Lys He Val Wing Leu Wing Asn Lys Glu Ser He 195 200 205 Val Ser Wing Gly Phe Phe Leu Lys Lys Leu Leu Asn He His Lys Asn 210 215 220 Wing Lys He He Pro Val Asp Ser Glu His Ser Wing He Phe Gln Cys 225 230 235 240 Leu Asp Asn Asn Lys Val Leu Lys Thr Lys Cys Leu Gln Asp Asn Phe 245 250 255 Being Lys He Asn Asn He Asn Lys He Phe Leu Cys Being Ser Gly Gly 260 265 270 Pro Phe Gln Asn Leu Thr Met Asp Glu Leu Lys Asn Val Thr Ser Glu 275 280 285 Asn Ala Leu Lys His Pro Lys Trp Lys Met Gly Lys Lys He Thr He 290 295 300 Asp Ser Ala Thr Met Met Asn Lys Gly Leu Glu Val He Glu Thr His 305 310 315 320 Phe Leu Phe Asp Val Asp Tyr Asn Asp He Glu Val He Val His Lys 325 330 335 Glu Cys He He His Ser Cys Val Glu Phe He Asp Lys Ser Val He 340 345 350 Being Gln Met Tyr Tyr Pro Asp Met Gln He Pro He Leu Tyr Ser Leu 355 360 365 Thr Trp Pro Asp Arg He Lys Thr Asn Leu Lys Pro Leu Asp Leu Wing 370 375 380 Gln Val Ser Thr Leu Thr Phe His Lys Pro Ser Leu Glu His Phe Pro 385 390 395 400 Cys He Lys Leu Wing Tyr Gln Wing Gly He Lys Gly Asn Phe Tyr Pro 405 410 415 Thr Val Leu Asn Wing Ser Asn Glu He Wing Asn Asn Leu Phe Leu Asn 420 425 430 Asn Lys He Lys Tyr Phe Asp He Ser Ser He He Ser Gln Val Leu 435 440 445 Glu Ser Phe Asn Ser Gln Lys Val Ser Glu Asn Ser Glu Asp Leu Met 450 455 460 Lys Gln He Leu Gln He His Ser Trp Wing Lys Asp Lys Wing Thr Asp 465 470 475 480 He Tyr Asn Lys His Asn Ser Ser 485 < 210 > 3 < 211 > 3872 < 212 > DNA < 213 > Plasmodium falciparum < 220 > < 221 > CDS < 222 > (126) .. (3740) < 220 > < 221 > gene < 222 > (1) .. (3870) < 220 > < 221 > MRNA < 222 > (1) .. (3870) < 400 > 3 ggtaatatac gtataatata tatataatat attcttacgt atgtatcatt tatgaatcat 60 aataatatte taaatttacc ttccgttttt gctcgatctt ctcattttcg tttcagcttt 120 tatca atg att ttt aat tat gtg ttt ttt aag aac ttt gta cca gtt gtt 170 Met He Phe Asn Tyr Val Phe Phe Lys Asn Phe Val Pro Val Val 1 '5 10 15 cta tac att etc ctt ata ata tat att aac tta aat ggc atg aat aat 218 Leu Tyr He Leu Leu He He Tyr He Asn Leu Asn Gly Met Asn Asn 20 25 30 aaa aat ca ata aaa here gaa aaa att tat ata aag aaa ttg aat agg 266 Lys Asn Gln He Lys Thr Glu Lys He Tyr He Lys Lys Leu Asn Arg 35 40 45 ttg tea agg aaa aat teg tta tgt agt tet aaa aat aaa ata gca tgc 314 Leu Ser Arg Lys Asn Ser Leu Cys Ser Ser Lys Asn Lys He Ala Cys 50 55 60 ttg ttc gat ata gga aat gat gat aat aga aat acg here tat ggc tat 362 Leu Phe Asp He Gly Asn Asp Asp Asn Arg Asn Thr Thr Tyr Gly Tyr 65 70 75 aat gtg aat gtt aaa aat gat gat att aat tec tta cta aaa aat aat 410 Asn Val Asn Val Lys Asn Asp Asp He Asn Ser Leu Leu Lys Asn Asn 80 85 90 95 tat agt aat aaa ttg tac atg gat aag agg aaa aat att aat aat gta 458 Tyr Ser Asn Lys Leu Tyr Met Asp Lys Arg Lys Asn He Asn Asn Val 100 105 110 att agt act aat aaa ata tet ggg tec att tea aat att tgt agt aga 506 I have been Thr Asn Lys I have been Gly Being I have Asn lie Cys Ser Arg 115 120 125 aat caa aaa gaa aat gaa caa aaa aga aat aaa ca a aga t a t t t t a act 554 Asn Gln Lys Glu Asn Glu Gln Lys Arg Asn Lys Gln Arg Cys Leu Thr 130 135 140 cat tgt falls act tat aat atg tea cat gaa cag gac aaa cta gct aat 602 Gln Cys His Thr Tyr Asn Met Ser His Glu Gln Asp Lys Leu Ala Asn 145 150 155 gat aat aat agg aat aat aaaat aat aat ttaat aat tta tta ttt ata aat 650 Asp Asn Asn Arg Asn Asn Lys Lys Asn Phe Asn Leu Leu Phe He Asn 160 165 170 175 tat ttt aat ttg aaa cga atg aaa aat tet ctt cta aat aaa gac aat 698 Tyr Phe Asn Leu Lys Arg Met Lys Asn Ser Leu Leu Asn Lys Asp Asn 180 185 190 ttc ttt tac tgt aaa gaa aaa aaa ttg tea ttt ctg cat aag gcc tat 746 Phe Phe Tyr Cys Lys Glu Lys Lys Leu Ser Phe Leu His Lys Ala Tyr 195 200 205 aaa aaa aaa aat tgc act ttt caa aat tat agt tta aaa aga aaa tet 794 Lys Lys Asn Cys Thr Phe Gln Asn Tyr Ser Leu Lys Arg Lys Ser 210 215 220 aat cgt gat tea cat aaa ttg ttt tet gga gaa ttt gac gat tat here 842 Asn Arg Asp Ser His Lys Leu Phe Ser Gly Glu Phe Asp Asp Tyr Thr 225 230 235 aat aat aat gct tta tat gaa tec gaa aaa aaa gaa tac att here cta 890 Asn Asn Asn Ala Leu Tyr Glu Ser Glu Lys Lys Glu Tyr He Thr Leu 240 245 250 255 aat aat aat aat aat aat aat aat aat aat aat aat aat aat aat aat 938 Asn Asn Asn Asn Lys Asn Asn Asn Asn Lys Asn Asn Asp Asn Lys Asn 260 265 270 aat gat aat aat gat tat aat aat aat aat agt tgt aat aat tta gga 986 Asn Asp Asn Asn Tyr Asn Asn Asn Asn Ser Cys Asn Asn Leu Gly 275 280 285 gag aga tec aat cat tat gat aat tat ggt gga gat aat aat aat cca 1034 Glu Arg Ser Asn His Tyr Asp Asn Tyr Gly Gly Asp Asn Asn Asn Pro 290 295 300 tgt aat aat aat aat gac aaa tat gat ata gga aaa tat ttc aaa cag 1082 Cys Asn Asn Asn Asn Asp Lys Tyr Asp He Gly Lys Tyr Phe Lys Gln 305 310 315 att aat acc ttt att aat att gat gaa tat aaa act ata tat ggt gat 1130 He Asn Thr Phe He Asn He Asp slu Tyr i.ys Thr He Tyr Gly Asp 320 325? 0 335 gaa ata tat aaa gaa ata tat gaa cta tat qta gaa aga aat att ect 1178 Glu He Tyr Lys Glu He Tyr Glu Leu Tyr Val Glu Arg Asn He Pro 340 34S 350 gaa tat tat gaa cga aaa tat ttt tea g * '-.at att aaa aag agt gtc 1226 Glu Tyr Tyr Glu Arg Lys Tyr Phe Ser Cía. esp He Lys Lys Ser Val 355 360 365 cta ttt gat ata gat aaa tat aat gat »j« aa ttt gaa aaa gct ata 1274 Leu Phe Asp He Asp Lys Tyr Asn Asp Glu Phe Glu Lys Ala He 370 375 380 aaa gaa gaa ttt ata aat aat gga gtt fftfe att aat aat ata gat aat 1322 Lys Glu Glu Phe He Asn Asn Gly VaJ "t tie Asn Asn He Asp Asn 385 390 395 here tat tat aaa aaa gaa aat att ttc * ata atg aaa aag ata tta cat 1370 Thr Tyr Tyr Lys Lys Glu Asn He Leu tie Met Lys Lys He Leu His 400 405 410 415 tat ttc cca tta tta aaa tta att as'- aat cca tea gat tta aaa aag 1418 Tyr Phe Pro Leu Leu Lys Leu He Asn Asn Pro Ser Asp Leu Lys Lys 420 425 430 tta aaa aaa caa tat tta ect tta tta gca cat gaa tta aaa ata ttt 1466 Leu Lys Lys Gln Tyr Leu Pro Leu Leu Wing His Glu Leu Lys He Phe 435 440 445 tta ttt ttt att gta aat ata here gga ggt cat ttt tec tet gtt tta 1514 Leu Phe Phe He Val Asn He Thr Gly Gly His Phe Ser Ser Val Leu 450 455 460 age tet tta gaa att cata tta tta tta ttg tat att ttt aat caca cca 1562 Ser Ser Leu Glu He Gln Leu Leu Leu Leu Tyr He Phe Asn Gln Pro 465 470 475 tat gat aat gtt ata tat gat ata gga cat ca gca tat gta cat aag 1610 Tyr Asp Asn Val He Tyr Asp He Gly His Gln Wing Tyr Val His Lys 480 485 490 495 ata ttg acc gga aga aaa cta tta ttt cta tea tta aga aat aaa aaa 1658 He Leu Thr Gly Arg Lys Leu Leu Phe Leu Ser Leu Arg Asn Lys Lys 500 505 510 ggt att agt gga ttc cta aat att ttt gaa agt att tat gat aaa ttt 1706 Gly He Ser Gly Phe Leu Asn He Phe Glu Ser He Tyr Asp Lys Phe 515 520 525 ggg gct ggt falls agt tec act tea tta agt gct ata ca g g tat tat 1754 Gly Ala Gly His Ser Ser Thr Ser Leu Ser Ala He Gln Gly Tyr Tyr 530 535 540 gaa gcc gag tgg ca gtg aag aat aaa gaa aaa tat gga aat gga gat 1802 Glu Wing Glu Trp Gln Val Lys Asn Lys Glu Lys Tyr Gly Asn Gly Asp 545 550 555 ata gaa ata agt gat aac gca aat gtc acg aat aat gaa agg ata ttt 1850 He Glu He Ser Asp Asn Ala Asn Val Thr Asn Asn Glu Arg He Phe 560 565 570 575 caa aaa gga ata falls aat gat aat aat att aac aat aat att aat aat 1898 Gln Lys Gly He His Asn Asp Asn Asn He Asn Asn Asn He Asn Asn 580 585 590 aat aat tat ate aat ect tea gat gtg gta gga aga gaa aat acg aat 1946 Asn Asn Tyr He Asn Pro Being Asp Val Val Gly Arg Glu Asn Thr Asn 595 600 605 gta cca aat gta cga aat gat aac cat aac gtg gat aaa gta falls att 1994 Val Pro Asn Val Arg Asn Asp Asn His Asn Val Asp Lys Val His He 610 615 620 gct att ata gga gat ggt ggt tta here ggt gga atg gca tta gaa gcg 2042 Wing He He Gly Asp Gly Gly Leu Thr Gly Gly Met Wing Leu Glu Wing 625 630 635 tta aat tat att tea ttc ttg aat tet aaa att tta att att tat aat 2090 Leu Asn Tyr He Ser Phe Leu Asn Ser Lys He Leu He He Tyr Asn 640 645 650 655 gat aac gga ca gtt tet tta cca here aat gcc gta agt ata tea ggt 2138 Asp Asn Gly Gln Val Ser Leu Pro Thr Asn Ala Val Ser He Ser Gly 660 665 670 aat aga ect ata ggt tet ata tea gat cat tta cat tat ttt gtt tet 2186 Asn Arg Pro He Gly Ser He Be Asp His Leu His Tyr Phe Val Ser 675 680 685 aat ata gaa gca aat gct ggt gat aat aaa tta teg aaa aat gca aaa 2234 Asn He Glu Wing Asn Wing Gly Asp Asn Lys Leu Ser Lys Asn Wing Lys 690 695 700 gag aat aat att ttt gaa aat ttg aat tat gat tat att ggt gtt gtg 2282 Glu Asn Asn He Phe Glu Asn Leu Asn Tyr Asp Tyr He Gly Val Val 705 710 715 aat ggt aat aat here gaa gag etc ttt aaa gta tta aat aat ata aaa 2330 Asn Gly Asn Asn Thr Glu Glu Leu Phe Lys Val Leu Asn Asn He Lys 720 725 730 735 gaa aat aaa tta aaa aga gct act gtt ctt cat gta cgt here aaa aaa 2378 Glu Asn Lys Leu Lys Arg Wing Thr Val Leu His Val Arg Thr Lys Lys 740 745 750 teg aat gat ttt ata aat tea aag agt cca ata agt ata ttg falls tet 2426 Ser Asn Asp Phe He Asn Ser Lys Ser Pro He Ser He Leu His Ser 755 760 765 ata aag aaa aat gag att ttc ect ttc gat ata act ata tta aat gga 2474 He Lys Lys Asn Glu He Phe Pro Phe Asp Thr Thr He Leu Asn Gly 770 775 780 aat att cat aag gag aac aag ata gaa gaa gag aaa aat gtg tet tea 2522 Asn He His Lys Glu Asn Lys He Glu Glu Glu Lys Asn Val Ser Ser 785 790 795 tet here aag tat gat gta aat aat aat aat aat aat aat gat aat 2570 be Thr Lys Tyr Asp Val Asn Asn Lys Asn Asn Lys Asn Asn Asp Asn 800 805 810 815 agt gaa att ata aaa tat gaa gat atg ttt tea aaa gag acg ttc here 2618 Ser Glu He He Lys Tyr Glu Asp Met Phe Ser Lys Glu Thr Phe Thr 820 825 830 gat tat ata aat gaa atg tta aaa tat tta aag aaa gat aga aat 2666 Asp He Tyr Thr Asn Glu Met Leu Lys Tyr Leu Lys Lys Asp Arg Asn 835 840 845 ata ata ttc cta tet ecc gct atg tta gga gga tea gga ttg gtt aaa 2714 He He Phe Leu Ser Pro Wing Met Leu Gly Gly Ser Gly Leu Val Lys 850 855 860 att agt gag cgt tat cca aat aat gta tat gat gta ggt ata gca gaa 2762 He Be Glu Arg Tyr Pro Asn Asn Val Tyr Asp Val Gly He Wing Glu 865 870 875 ca cat cat tet gta act tca gca gca gct atg gca atg aat aag aaa tta 2810 Gln His Ser Val Thr Phe Wing Wing Wing Met Wing Met Asn Lys Lys Leu 880 885 890 895 aaa ata cata tta tgt ata tat teg acc ttt tta caa aga gca tat gat 2858 Lys He Gln Leu Cys He Tyr Ser Thr Phe Leu Gln Afg Ala Tyr Asp 900 905 910 ca ata att ata cat gat ctt aat tta ca ata ata ata ect tta aag gtt ata 2906 Gln He He His Asp Leu Asn Leu Gln Asn He Pro Leu Lys Val He 915 920 925 att gga aga agga gga tta gta gga gag gat ggg gca here cat ca ggt 2954 He Gly Arg Ser Gly Leu Val Gly Glu Asp Gly Ala Thr His Gln Oly 930 935 940 ata tat gat tta tet tat ctt ggg here ctt aac aat gca tat ata ata 3002 He Tyr Asp Leu Ser Tyr Leu Gly Thr Leu Asn Asn Ala Tyr He He 945 950 955 tet cea agt aat ca gtt gat ttg aaa aga gct ctt agg ttt gct tat 3050 Ser Pro As Asn Gln Val Asp Leu Lys Arg Ala Leu Arg Phe Ala Tyr 960 965 970 975 tta gat aag gac cat tet gtg tat ata cgt ata ecc aga aga aac ata 3098 Leu Asp Lys Asp His Ser Val Tyr He Arg He Pro Arg Met Asn He 980 985 990 tta agt gat aag tac atg aaa gga tat ttg aac att cat atg aaa aat 3146 Leu Ser Asp Lys Tyr Met Lys Gly Tyr Leu Asn He His Met Lys Asn 995 1000 1005 gag age aaa aat ate gat gta aac gtg gat ata aac gat gat gat gat 3194 Glu Ser Lys Asn He Asp Val Asn Val Asp He Asn Asp Asp Val Asp 1010 1015 1020 aaa tat agt gaa gaa tat atg gac gat gat aat ttt ata aaa teg ttt 3242 Lys Tyr Ser Glu Glu Tyr Met Asp Asp Asp Asn Phe He Lys Ser Phe 1025 1030 1035 att gga aaa tet aga att att aaa atg gat aat gaa aat aat aat here 3290 He Gly Lys Being Arg He He Lys Met Asp Asn Glu Asn Asn Asn Thr 1040 1045 1050 1055 aat gaa cat tat tea age aga gga gat here cag here aaa aaa aaa aaa 3338 Asn Glu His Tyr Ser Ser Arg Gly Asp Thr Oln Thr Lys Lys Lys Lys 1060 1065 1070 gtt tgt ate ttt aac atg ggt agt atg ctt ttt aat gta att aat gct 3386 Val Cys He Phe Asn Met Gly Ser Met Leu Phe Asn Val He Asn Wing 1075 1080 1085 ata aaa gaa att gaa aaa gaa caa tat att tea cat aat tat tet ttt 3434 He Lys Glu He Glu Lys Glu Gln Tyr He Ser His Asn Tyr Ser Phe 1090 1095 1100 tea att gtt gat atg ata ttt tta aat ect tta gat aaa ata atat ata 3482 Ser He Val Asp Met He Phe Leu Asn Pro Leu Asp Lys Asn Met He 1105 1110 1115 gat cat gta ata aaa caa aat aaa cat ca tat tat att tat tat gaa 3530 Asp His Val He Lys Gln Asn Lys His Oln Tyr Leu lie Thr Tyr Glu 1120 1125 1130 1135 gat aat act ata ggt ggt ttt tet here cat ttc aat aat tat tta ata 3578 Asp Asn Thr He Gly Oly Phe Ser Thr His Phe Asn Asn Tyr Leu He 1140 1145 1150 gaa aat aat tat att here aaa cat aac tta tat gtt cat aat att tat 3626 Glu Asn Asn Tyr He Thr Lys His Asn Leu Tyr Val His Asn He Tyr 1155 1160 1165 tta tat aat gag cca att gaa cat gca tet ttt aag gat caá caa gaa 3674 Leu Ser Asn Glu Pro He Glu His Wing Being Phe Lys Asp Gln Gln Glu 1170 1175 1180 gtc gtc aaa atg gat aaa tgt agt ctt gtc aat aga att aaa tat 3722 Val Val Lys Met Asp Lys Cys Ser Leu Val Asn Arg He Lys Asn Tyr 1185 1190 1195 ctt aaa aat aat ect here tgatgtaaga taaatatata tttctaaaat 3770 Leu Lys Asn Asn Pro Thr 1200 1205 tatttttttt ttatacttta atgtgtacaa taaaatatat atctaaatat attttatttg 3830tacgcttttt tttttttttt tttaattgtt atttttgtat at 3872 < 210 > 4 < 211 > 1205 < 212 > PRT < 213 > Plasmodium falciparum < 400 > 4 Met He Phe Asn Tyr Val Phe Phe Lys Asn Phe Val Pro Val Val Leu 1 5 10 15 Tyr He Leu Leu He He Tyr He Asn Leu Asn Gly Met Asn Asn Lys 20 25 30 Asn Gln He Lys Thr Olu Lys He Tyr He Lys Lys Leu Asn Arg Leu 35 40 45 Ser Arg Lys Asn Ser Leu Cys Ser Ser Lys Asn Lys He Ala Cys Leu 50 55 60 Phe Asp He Gly Asn Asp Asp Asn Arg Asn Thr Thr Tyr Cly Tyr Asn 65 70 75 80 Val Asn Val Lys Asn Asp Asp He Asn Ser Leu Leu Lys Asn Asn Tyr 85 90 95 Be Asn Lys Leu Tyr Met Asp Lys Arg Lys Asn He Asn Asn Val He 100 105 110 Be Thr Asn Lys Be Ser Oly Be He Be Asn He Cys Ser Arg Asn 115 120 12'5 Oln Lys slu Asn Olu Oln Lys Arg Asn Lys Oln Arg Cys Leu Thr sln 130 135 140 Cys His Thr Tyr Asn Met Ser His Glu Gln Asp Lys Leu Wing Asn Asp 145 150 155 160 Asn Asn Arg Asn Asn Lys Lys Asn Phe Asn Leu Leu Phe He Asn Tyr 165 170 175 Phe Asn Leu Lys Arg Met Lys Asn Ser Leu Leu Asn Lys Asp Asn Phe 180 185 190 Phe Tyr Cys Lys Glu Lys Lys Leu Ser Phe Leu His Lys Wing Tyr Lys 195 200 205 Lys Lys Asn Cys Thr Phe Gln Asn Tyr Ser Leu Lys Arg Lys Ser Asn 210 215 220 Arg Asp Ser His Lys Leu Phe Ser Gly Glu Phe Asp Asp Tyr Thr Asn 225 230 235 240 Asn Asn Ala Leu Tyr Glu Ser Glu Lys Lys Glu Tyr He Thr Leu Asn 245 250 255 Asn Asn Asn Lys Asn Asn Asn Asn Lys Asn Asn Asp Asn Lys Asn Asn 260 265 270 Asp Asn Asn Asp Tyr Asn Asn Asn Asn Ser Cys Asn Asn Leu Gly Glu 275 280 285 Arg Ser Asn His Tyr Asp Asn Tyr Gly Gly Asp Asn Asn Asn Pro Cys 290 295 300 Asn Asn Asn Asn Asp Lys Tyr Asp He Gly Lys Tyr Phe Lys Gln He 305 310 315 320 Asn Thr Phe He Asn He Asp Glu Tyr Lys Thr He Tyr Gly Asp Glu 325 330 335 He Tyr Lys Glu He Tyr Glu Leu Tyr Val Glu Arg Asn He Pro Glu 340 345 350 Tyr Tyr Glu Arg Lys Tyr Phe Ser Glu Asp He Lys Lys Ser Val Leu 355 360 365 Phe Asp He Asp Lys Tyr Asn Asp Val Glu Phe Glu Lys Ala He Lys 370 375 380 Glu Glu Phe He Asn Asn Gly Val Tyr He Asn Asn He Asp Asn Thr 385 390 395 400 Tyr Tyr Lys Lys Glu Asn He Leu He Met Lys Lys He Leu His Tyr 405 410 415 Phe Pro Leu Leu Lys Leu He Asn Asn Pro Ser Asp Leu Lys Lys Leu 420 425 430 Lys Lys Gln Tyr Leu Pro Leu Leu Wing His Glu Leu Lys He Phe Leu 435 440 445 Phe Phe He Val Asn He Thr Gly Oly His Phe Ser Ser Val Leu Ser 450 455 460 Ser Leu slu He Gln Leu Leu Leu Leu Tyr He Phe Asn Gln Pro Tyr 465 470 475 480 Asp Asn Val He Tyr Asp He Oly His Gln Wing Tyr Val His Lys He 485 490 495 Leu Thr Gly Arg Lys Leu Leu Phe Leu Ser Leu Arg Asn Lys Lys Gly 500 505 510 He Be Gly Phe Leu Asn He Phe Glu Be He Tyr Asp Lys Phe Gly 515 520 525 Ala Gly His Ser Ser Thr Ser Leu Ser Ala He Gln Gly Tyr Tyr Glu 530 535 540 Wing Glu Trp Gln Val Lys Asn Lys Glu Lys Tyr Gly Asn Gly Asp He 545 550 555 560 Glu He Ser Asp Asn Wing Asn Val Thr Asn Asn Glu Arg He Phe Gln 565 570 '575 Lys Gly He His Asn Asp Asn Asn He Asn Asn Asn He Asn Asn Asn 580 585 590 Asn Tyr He Asn Pro Being Asp Val Val Gly Arg Glu Asn Thr Asn Val 595 600 605 Pro Asn Val Arg Asn Asp Asn His Asn Val Asp Lys Val His He Wing 610 615 620 He He sly Asp Oly Oly Leu Thr Oly sly Met Ala Leu Glu Ala Leu 625 630 635 640 Asn Tyr He Ser Phe Leu Asn Ser Lys He Leu He He Tyr Asn Asp 645 650 655 Asn Gly Gln Val Ser Leu Pro Thr Asn Ala Val Ser Be Ser Gly Asn 660 665 670 Arg Pro He Gly Ser He Asp His Leu His Tyr Phe Val Ser Asn 675 680 685 He Glu Wing Asn Wing Gly Asp Asn Lys Leu Ser Lys Asn Wing Lys Glu 690 695 700 Asn Asn He Phe Glu Asn Leu Asn Tyr Asp Tyr He Gly Val Val Asn 705 710 715 720 Gly Asn Asn Thr Glu Glu Leu Phe Lys Val Leu Asn Asn He Lys Glu 725 730 735 Asn Lys Leu Lys Arg Wing Thr Val Leu His Val Arg Thr Lys Lys Ser 740 745 750 Asn Asp Phe He Asn Ser Lys Ser Pro He Ser He Leu His Ser He 755 760 765 Lys Lys Asn Glu He Phe Pro Phe Asp Thr He Leu Asn Gly Asn 770 775 780 He His Lys Glu Asn Lys He Glu Glu Olu Lys Asn Val Ser Ser Ser 785 790 795 800 Thr Lys Tyr Asp Val Asn Asn Lys Asn Asn Lys Asn Asn Asp Asn Ser 805 810 815 slu He He Lys Tyr Glu Asp Met Phe Ser Lys slu Thr Phe Thr Asp 820 825 830 He Tyr Thr Asn Glu Met Leu Lys Tyr Leu Lys Lys Asp Arg Asn He 835 840 845 He Phe Leu Ser Pro Wing Met Leu Gly Gly Ser Gly Leu Val Lys He 850 855 860 Ser slu Arg Tyr Pro Asn Asn Val Tyr Asp Val Olye Wing Glu Gln 865 870 875 880 His Ser Val Thr Phe Wing Wing Wing Met Wing Met Asn Lys Lys Leu Lys 885 890 895 He Gln Leu Cys He Tyr Ser Thr Phe Leu Gln Arg Ala Tyr Asp Oln 900 905 910 He He His Asp Leu Asn Leu Oln Asn He Pro Leu Lys Val He He 915 920 925 Gly Arg Ser sly Leu Val Gly Glu Asp Gly Ala Thr His Gln Gly He 930 935 940 Tyr Asp Leu Ser Tyr Leu Gly Thr Leu Asn Asn Wing Tyr He He Ser 945 950 955 960 Pro As Asn Gln Val Asp Leu Lys Arg Ala Leu Arg Phe Ala Tyr Leu 965 970 975 Asp Lys Asp His Ser Val Tyr He Arg He Pro Arg Met Asn He Leu 980 985 990 Being Asp Lys Tyr Met Lys Gly Tyr Leu Asn He His Met Lys Asn Glu 995 1000 1005 Ser Lys Asn He Asp Val Asn Val Asp He Asn Asp Asp Val Asp Lys 1010 1015 1020 Tyr Ser slu Olu Tyr Met Asp Asp Asp Asn Phe He Lys Ser Phe He 025 1030 1035 1040 Oly Lys Ser Arg He He Lys Met Asp Asn Glu Asn Asn Asn Thr Asn 1045 1050 1055 Glu His Tyr Ser Ser Arg Gly Asp Thr Gln Thr Lys Lys Lys Lys Val 1060 1065 1070 Cys He Phe Asn Met Gly Ser Met Leu Phe Asn Val He Asn Ala He 1075 1080 1085 Lys Glu He slu Lys Glu Gln Tyr He Ser His Asn Tyr Ser Phe Ser 1090 1095 1100 He Val Asp Met He Phe Leu Asn Pro Leu Asp Lys Asn Met He Asp 105 1110 1115 1120 His Val He Lys Gln Asn Lys His Gln Tyr Leu He Thr Tyr Glu Asp 1125 1130 1135 Asn Thr He Gly Gly Phe Ser Thr His Phe Asn Asn Tyr Leu He Glu 1140 1145 1150 Asn Asn Tyr He Thr Lys His Asn Leu Tyr Val His Asn He Tyr Leu 1155 1160 1165 Ser Asn Glu Pro He Glu His Wing Ser Phe Lys Asp Gln Gln Glu Val 1170 1175 1180 Val Lys Met Asp Lys Cys Ser Leu Val Asn Arg He Lys Asn Tyr Leu 185 1190 1195 1200 Lys Asn Asn Pro Thr 1205 < 210 > 5 < 211 > 3147 < 212 > DNA < 213 > Plasmodium falciparum < 220 > < 221 > CDS < 222 > (199). 2670 < 400 > 5 tttcattttt ctttacccac atatatatat atatatatat aatatatata tataatatta 60 tatatttgat atatgattta aaattgtaac ataaaaaaaa taattatatt aaatatgtgt 120 atacatctcc aacatataaa tattattttt tattattatt tttttttttt ttttteataa 180 tgcctgaata accacaaa atg agt tat ata aaa aga ctg att ctt ttt atg 231 Met Ser Tyr He Lys Arg Leu He Leu Phe Met 1 5 10 tta ctg ttt tat tet cat gta aaa att aaa aaa tta ttt att aaa att 279 Leu Leu Phe Tyr Ser His Val Lys He Lys Lys Leu Phe He Lys He 15 20 25 tet aat gta aac ata ttt ttt gca gaa gca aag aaa aat gga aaa aag 327 As Asn Val Asn He Phe Phe Wing Glu Wing Lys Lys Asn Gly Lys Lys 30 35 40 gaa ttc ttt ctt ttt tta cta aat ata aaa aaa aat age caa cag aaa 375 Glu Phe Phe Leu Phe Leu Leu Asn He Lys Lys Asn Ser Gln Gln Lys 45 50 55 aaa act tat cat att acc aaa agg aat acc ata aat aaa agt gat ttt 423 Lys Thr Tyr His He Thr Lys Arg Asn Thr He Asn Lys Ser Asp Phe 60 65 70 75 tta tat tet tta cta aat gaa gaa ggg aat tet tea aaa aag gaa tat 471 Leu Tyr Ser Leu Leu Asn Glu Glu Gly Asn Ser Ser Lys Lys Glu Tyr 80 85 90 aaa aat tta aaa gat gaa gaa aaa tat aat ate ata ata aat ata aaa 519 Lys Asn Leu Lys Asp Glu Glu Lys Tyr Asn He He Gln Asn He Lys 95 100 105 aaa tat tgt gaa tgt act aaa aaa tat aaa agg etc cca here cga gaa 567 Lys Tyr Cys Glu Cys Thr Lys Lys Tyr Lys Arg Leu Pro Thr Arg Glu 110 115 120 gta gtt att gga aat gtt aaa att gga gga aat aat aaa ata gct att 615 Val Val He Gly Asn Val Lys He sly sly Asn Asn Lys He Wing He 125 130 135 ca at act atg gct age tgt gat aga aat gta gaa gag tgt gta tat 663 Oln Thr Met Wing Cys Asp Thr Arg Asn Val Clu Olu Cys Val Tyr 140 145 150 155 ca att att aaa tgt aaa gat ttg ggt gct gac att gta agg ttg act 711 sln He Arg Lys Cys Lys Asp Leu Oly Wing Asp He Val Arg Leu Thr 160 165 170 gtt ca gga gtt ca g gaa gca ca gct agt tat cat att aaa gaa aaa 759 Val Oln Oly Val Oln slu Ala Gln Ala Ser Tyr His He Lys Glu Lys 175 180 185 tta tta tet gaa aat gta aat ate cca tta gta gca gat att cat ttt 807 Leu Leu Ser slu Asn Val Asn He Pro Leu Val Wing Asp He His Phe 190 195 200 aat ect aaa ata gct tta atg gca gct gat gtg ttt gaa aaa att cga 855 Asn Pro Lys He Ala Leu Met Ala Wing Asp Val Phe Glu Lys He Arg 205 210 215 gtg aat cca gga aat tat gtt gat gga aga aaa aaa tgg ata gat aaa 903 Val Asn Pro Gly Asn Tyr Val Asp Gly Arg Lys Lys Trp He Asp Lys 220 225 230 235 gtt tat aaa act aaa gaa gaa ttt gat gaa ggg aaa tta ttt ata aaa 951 Val Tyr Lys Thr Lys Glu Glu Phe Asp Glu Gly Lys Leu Phe He Lys 240 245 250 gaa aaa ttt gta cca tta att gaa aaa tgt aaa aga tta aat aga aga gca 999 Glu Lys Phe Val Pro Leu He Glu Lys Cys Lys Arg Leu Asn Arg Ala 255 260 265 ata aga att gga here aat cat gga tec ctt tea tet cga gta tta tea 1047 He Arg He Oly Thr Asn His Oly Ser Leu Ser Ser Arg Val Leu Ser 270 275 280 tat tat gga gat here cca tta ggt atg gta gaa teg gct ttt gag ttt 1095 Tyr Tyr Gly Asp Thr Pro Leu Gly Met Val Glu Ser Wing Phe Glu Phe 285 290 295 tet gat tta tgt att gaa aac aat ttt tac aat ctt gtt ttt tet tet atg 1143 Ser Asp Leu Cys He Glu Asn Asn Phe Tyr Asn Leu Val Phe Ser Met 300 305 310 315 aaa gct tet aat gct tat gtt atg ata cata tet tat aga tta tta gta 1191 Lys Ala Ser Asn Ala Tyr Val Met He Gln Ser Tyr Arg Leu Leu Val 320 325 330 tet aaa caa tat gaa aga aat atg atg ttc ect ata cat tta gga gtt 1239 Ser Lys Gln Tyr Glu Arg Asn Met Met Phe Pro He His Leu Gly Val 335 340 345 here gaa gca gga ttt ggt gat aat gga aga ata aaa tet tat tta ggt 1287 Thr Glu Wing Gly Phe Gly Asp Asn Gly Arg He Lys Ser Tyr Leu Gly 350 355 360 ata gga tet tta tta tat gat ggt ata gga gat acc att cgt ata tec 1335 He Oly Ser Leu Leu Tyr Asp sly He Gly Asp Thr He Arg He Ser 365 370 375 tta here gaa gat ect tgg gaa gag tta act ect tgt aaa aaa tta gtt 1383 Leu Thr Glu Asp Pro Trp Glu Glu Leu Thr Pro Cys Lys Lys Leu Val 380 385 390 395 gaa aat tta aag aaa aga ata ttt tat aat gaa aat ttt aaa gaa gat 1431 Olu Asn Leu Lys Arg He Phe Tyr Asn Glu Asn Phe Lys Glu Asp 400 405 410 aat gaa tta aaa aat aat gaa atg gat acc aaa aat cta tta aat ttt 1479 Asn Glu Leu Lys Asn Asn Glu Met Asp Thr Lys Asn Leu Leu Asn Phe 415 420 425 gaa gaa aat tat cga aat ttt aat aat ata aaa aaa aga aat gta gaa 1527 Glu Glu Asn Tyr Arg Asn Phe Asn Asn He Lys Lys Arg Asn Val Glu 430 435 440 aaa aat aat aat gta tta cat gaa gag tgc act ata ggt aat gta gta 1575 Lys Asn Asn Asn Val Leu His Glu Glu Cys Thr He Gly Asn Val Val 445 450 455 acc ata aaa gag tta gaa gat tet ctg ca ata att ttt aaa gat tta aat 1623 Thr He Lys Glu Leu Glu Asp Ser Leu Gln He Phe Lys Asp Leu Asn 460 465 470 475 tta gaa gta gat tea aat gga aat ttg aaa aag gga gcc aaa here act 1671 Leu Glu Val Asp Ser Asn Gly Asn Leu Lys Lys Gly Wing Lys Thr Thr 480 485 490 gat atg gtt att ata aat gat ttt cat aat ata ata aat tta gga aaa 1719 Asp Met Val He He As Asp Phe His Asn He Thr Asn Leu Gly Lys 495 500 505 aaa act gtg gat aaa tta atg ca gtg gga att aat ata gta gtt ca 1767 Lys Thr Val Asp Lys Leu Met Gln Val Gly He Asn He Val Val Gln 510 515 520 tat gaa cca cat aat ata gaa ttt ata gaa aaa atg gaa cca aat aat 1815 Tyr Glu Pro His Asn He Glu Phe He Glu Lys Met Glu Pro Asn Asn 525 530 535 gat aat aat aat aat aat aat aat aat ata ata tta tat tat gtg gat 1863 Asp Asn Asn Asn Asn Asn Asn Asn Asn Asn He Leu Phe Tyr Val Asp 540 545 550 555 ata aaa aat att atg aac agt tea gaa aaa aat att aa a tta agt aat 1911 He Lys Asn He Met Asn Ser Ser Glu Lys Asn He Lys Leu Ser Asn 560 565 570 tet aaa gga tat gga tta att tta aac gga aaa gaa gat ata ata acc 1959 Ser Lys Gly Tyr Gly Leu He Leu Asn Gly Lys Glu Asp He Oln Thr 575 580 585 ata aaa aaa ata aaa gaa tta aat cgt cgt ect tta ttc att cta tta 2007 He Lys Lys He Lys Glu Leu Asn Arg Arg Pro Leu Phe He Leu Leu 590 595 600 aaa tea gat aac ata tat gaa cat gta tta ata acc aga aga att aat 2055 Lys Ser Asp Asn He Tyr Glu His Val Leu He Thr Arg Arg He Asn 605 610 615 gaa ctt tta caá tec tta aat ata aat ata ect tat ata cat tat gtt 2103 Glu Leu Leu Gln Ser Leu Asn He Asn He Pro Tyr He His Tyr Val 620 625 630 635 gat att aat tea aac aat tat gat gat ata tta gtt aat tea here tta 2151 Asp He Asn Ser Asn Asn Tyr Asp Asp He Leu Val Asn Ser Thr Leu 640 645 650 tat gca gga agt tgt ttg atg gat tta atg ggg gat ggt ctt att gtt 2199 Tyr Wing Gly Ser Cys Leu Met Asp Leu Met Gly Asp Gly Leu He Val 655 660 665 aac gta act aat gat gtt ctt here aat aaa aaa aag ata gaa aaa aa 2247 Asn Val Thr Asn Asp Val Leu Thr Asn Lys Lys Lys He Glu Thr Lys 670 675 680 tat gat gaa aaa gaa gaa gta gag gag gaga gga aac aat aaa gat att 2295 Tyr Asp Glu Lys Glu Glu Val Glu Glu Glu Gly Asn Asn Lys Asp He 685 690 695 cat aga ctt ttg age aga gtt gta tta aat tea ttt tta here tta aat 2343 His Arg Leu Leu Ser Arg Val Ala Leu Asn Ser Phe Leu Thr Leu Asn 700 705 710 715 att tta ca gat gat aga ata cgt tta ttt aaa here gat tat ata gcc 2391 He Leu Gln Asp Thr Arg He Arg Leu Phe Lys Thr Asp Tyr He Wing 720 725 730 tgc cca tet tgt gga aga act tta ttt aat ata caa gaa act act aaa 2439 Cys Pro Ser Cys Gly Arg Thr Leu Phe Asn He Gln Glu Thr Thr Lys 735 740 745 aaa att atg aaa tta here ggg s tta aaa ggc gtt aaa att gca gtc 2487 Lys He Met Lys Leu Thr Gly His Leu Lys Gly Val Lys He Ala Val 750 755 760 atg gga tgt att gtt aat ggt ata gga gaa atg gca gat gca cat ttt 2535 Met Gly Cys He Val Asn Gly He Gly Glu Met Wing Asp Wing His Phe 765 770 775 ggt tat gtt ggt agt gca ect aaa aaa att gat tta tat tat ggt aaa 2583 Gly Tyr Val Gly Ser Wing Pro Lys Lys He Asp Leu Tyr Tyr Gly Lys 780 785 790 795 gag tta gta gaa aga aat ata ect gag gaa gaa gct tgt gat aaa ttg 2631 Olu Leu Val Glu Arg Asn He Pro Glu Olu Glu Wing Cys Asp Lys Leu 800 805 810 ata gaa tta att aaa aaa cat aac aaa tgg aaa gat cca taaattgaat 2680 He Glu Leu He Lys Lys His Asn Lys Trp Lys Asp Pro 815 820 atggacaagt atttatttat ttatttatct tatatataat atattataaa tttttegatg 2740 tatttttcct tttaaaattt tatttttttt ttattttttt ttttgaagta atatttataa 2800 tgeatacata atattaaaat gtgtattata taataatatc attttattgt tattttaaaa 2860 gactaatacc aagaacaatt ttttaataat cattcttata acttgttaaa tatatatata 2920 tatatatata tatttattta tttatattta tatttattta tttttggtat atgaaaagta 2980 aaaatataat aatttaaaag tatttacaaa ataaataata ttatatatct gtttttatat 3040 atatgttaat ggaaaaggag aaaataaata aataaaacaa acaaaataac atatatatat 3100 atatatatat actgaatgag aaagaaaaaa aaaagaaaag gatacga 3147 < 210 > 6 < 211 > 824 < 212 > PRT < 213 > Plasmodium falciparum < 400 > 6 Met Ser Tyr He Lys Arg Leu He Leu Phe Met Leu Leu Phe Tyr Ser 1 5 10 15 His Val Lys He Lys Lys Leu Phe He Lys He Ser As Asn Val Asn He 20 25 30 Phe Phe Wing Glu Wing Lys Lys Asn Gly Lys Lys Glu Phe Phe Leu Phe 35 40 45 Leu Leu Asn He Lys Lys Asn Ser Gln Oln Lys Lys Thr Tyr His He 50 55 60 Thr Lys Arg Asn Thr He Asn Lys Ser Asp Phe Leu Tyr Ser Leu Leu 65 70 75 80 Asn Glu Glu Gly Asn Ser Ser Lys Lys Glu Tyr Lys Asn Leu Lys Asp 85 90 95 Glu Glu Lys Tyr Asn He He Gln Asn He Lys Lys Tyr Cys Glu Cys 100 105 110 Thr Lys Lys Tyr Lys Arg Leu Pro Thr Arg Glu Val Val He Gly Asn 115 120 125 Val Lys He Gly Gly Asn Asn Lys He Wing He Gln Thr Met Wing Ser 130 135 140 Cys Asp Thr Arg Asn Val Olu Glu Cys Val Tyr Gln He Arg Lys Cys 145 150 155 160 Lys Asp Leu sly Wing Asp He Val Arg Leu Thr Val Oln Oly Val Gln 165 170 175 Glu Ala Gln Ala Ser Tyr His He Lys Olu Lys Leu Leu Ser Olu Asn 180 185 190 Val Asn He Pro Leu Val Wing Asp He His Phe Asn Pro Lys He Wing 195 200 205 Leu Met Ala Ala Asp Val Phe Glu Lys He Arg Val Asn Pro Gly Asn 210 215 220 Tyr Val Asp Gly Arg Lys Lys Trp He Asp Lys Val Tyr Lys Thr Lys 225 230 235 240 Glu Glu Phe Asp Glu Gly Lys Leu Phe He Lys Glu Lys Phe Val Pro 245 250 255 Leu He Glu Lys Cys Lys Arg Leu Asn Arg Wing He Arg He Gly Thr 260 265 '270 Asn His Gly Ser Leu Ser Ser Arg Val Leu Ser Tyr Tyr sly Asp Thr 275 280 285 Pro Leu sly Met Val Glu Be Wing Phe Glu Phe Ser Asp Leu Cys He 290 295 300 Glu Asn Asn Phe Tyr Asn Leu Val Phe Ser Met Lys Ala Ser Asn Ala 305 310 315 320 Tyr Val Met He Gln Ser Tyr Arg Leu Leu Val Ser Lys sln Tyr Olu 325 330 335 Arg Asn Met Met Phe Pro He His Leu sly Val Thr slu Ala Gly Phe 340 345 350 Gly Asp Asn Gly Arg He Lys Ser Tyr Leu Gly He Gly Ser Leu Leu 355 360 365 Tyr Asp Gly He Gly Asp Thr He Arg He Ser Leu Thr Glu Asp Pro 370 375 380 Trp Glu Glu Leu Thr Pro Cys Lys Lys Leu Val Glu Asn Leu Lys Lys 385 390 395 400 Arg He Phe Tyr Asn Glu Asn Phe Lys Glu Asp Asn Glu Leu Lys Asn 405 410 415 Asn Glu Met Asp Thr Lys Asn Leu Leu Asn Phe Glu Glu Asn Tyr Arg 420 425 430 Asn Phe Asn Asn He Lys Lys Arg Asn Val Glu Lys Asn Asn Asn Val 435 440 445 Leu His Glu Glu Cys Thr He Gly Asn Val Val Thr He Lys Glu Leu 450 455 460 Glu Asp Ser Leu Oln He Phe Lys Asp Leu Asn Leu Glu Val Asp Ser 465 470 475 480 Asn Gly Asn Leu Lys Lys Gly Wing Lys Thr Thr Asp Met Val He He 485 490 495 Asn Asp Phe His Asn He Thr Asn Leu Gly Lys Lys Thr Val Asp Lys 500 505 510 Leu Met Gln Val Gly He Asn He Val Val Gln Tyr Glu Pro His Asn 515 520 525 He Glu Phe He Glu Lys Met Glu Pro Asn Asn Asp Asn Asn Asn Asn 530 535 540 Asn Asn Asn Asn Asn He Leu Phe Tyr Val Asp He Lys Asn He Met 545 550 555 560 Asn Be Ser Glu Lys Asn He Lys Leu Ser Asn Ser Lys sly Tyr Oly 565 570 575 Leu He Leu Asn Oly Lys Olu Asp He Oln Thr He Lys Lys He Lys 580 585 590 Olu Leu Asn Arg Arg Pro Leu Phe He Leu Leu Lys Ser Asp Asn He 595 600 605 Tyr Olu His Val Leu He Thr Arg Arg He Asn slu Leu Leu Oln Ser 610 615 620 Leu Asn He Asn He Pro Tyr He His Tyr Val Asp He Asn Ser Asn 625 630 635 640 Asn Tyr Asp Asp He Leu Val Asn Ser Thr Leu Tyr Ala Oly Ser Cys 645 650 655 Leu Met Asp Leu Met Gly Asp Cly Leu He Val Asn Val Thr Asn Asp 660 665 670 Val Leu Thr Asn Lys Lys Lys He Glu Thr Lys Tyr Asp Glu Lys Glu 675 680 685 Glu Val Glu Glu Glu Gly Asn Asn Lys Asp He His Arg Leu Leu Ser 690 695 700 Arg Val Ala Leu Asn Ser Phe Leu Thr Leu Asn He Leu Gln Asp Thr 705 710 715 '720 Arg He Arg Leu Phe Lys Thr Asp Tyr He Wing Cys Pro Ser Cys Gly 725 730 735 Arg Thr Leu Phe Asn He Gln Glu Thr Thr Lys Lys He Met Lys Leu 740 745 750 Thr Gly His Leu Lys Gly Val Lys He Wing Val Met Gly Cys He Val 755 760 765 Asn Oly He Gly Glu Met Wing Asp Wing His Phe Gly Tyr Val Gly Ser 770 775 780 Wing Pro Lys Lys He Asp Leu Tyr Tyr Gly Lys Glu Leu Val Glu Arg 785 790 795 800 Asn He Pro Glu Glu Glu Wing Cys Asp Lys Leu He Glu Leu He Lys 805 810 815 Lys His Asn Lys Trp Lys Asp Pro 820

Claims (18)

1. - DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO: 2 or an analog or derivative of the polypeptide according to SEQ ID NO: 2, wherein one or more amino acids have been omitted, added or replaced by other amino acids; where the enzymatic action of the polypeptide is retained, and said sequences originate from parasites; where the sequence variations that occur within the framework of natural strain variability are included.

2. DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO: 4 or an analog or derivative of the polypeptide according to SEQ ID NO: 4, wherein one or more amino acids have been omitted, added or replaced by other amino acids; where the enzymatic action of the polypeptide is retained, and said sequences originate from parasites; where the sequence variations that occur within the framework of natural strain variability are included.

3. DNA sequences encoding a polypeptide with the amino acid sequence shown in SEQ ID NO: 6 or an analog or derivative of the polypeptide according to SEQ ID NO: 6, wherein one or more amino acids have been omitted, added or replaced by other amino acids; where the enzymatic action of the polypeptide is retained.

4. - DNA sequence according to any of claims 1 to 3, further characterized in that it also comprises functional regulation signals, in particular promoters, operators, enhancers, ribosome binding sites.

5.- Sequence of DNA with the following subsequences: i) promoter that is active in viruses, eukaryotes and prokaryotes, and guarantees the formation of an RNA in the target tissue or in the target cells, to which it is directed; I) DNA sequences according to one of claims 1 to 3; iii) 3'-untranslated sequence which, in viruses, eukaryotes and prokaryotes, results in the addition of poly (A) residues at the 3 'end of the RNA.

6. Process for the production of transgenic viruses, eukaryotes and prokaryotes, to modify the isoprenoid content, characterized in that a DNA sequence is transferred according to claim 4 or 5, and it is incorporated into the virus genome, cells eukaryotic and prokaryotic, with or without the use of a vector. 1.

Transgenic systems, in particular plants and plant cells, characterized in that they contain one or more DNA sequences according to claims 1 to 5, as "extraneous" or "extra" DNA; and said sequences are expressed.

8. Expression vector, characterized in that it contains one or more DNA sequences in accordance with the claims 1 to 5.

9. Protein, characterized in that it is involved in the metabolic path of the 5-phosphate of 1-deoxy-D-xylulase, and a) is encoded by the DNA sequences SEQ ID NO. 1, 3 or 5; or b) is encoded by DNA sequences that hybridize with DNA sequences SEQ ID NO. 1, 3, 5, or fragments of these DNA sequences, in the region of DNA encoding the mature protein.

10. A protein according to claim 9, characterized in that it can be obtained from the culture supernatants of parasites, or altered parasites, and purified by chromatographic and electrophoretic methods.

11. Protein according to any of claims 9 and 10, further characterized in that a) is the product of viral, prokaryotic or eukaryotic expression of exogenous DNA; b) is encoded by the sequences SEQ ID NO: 1, 3 or 5, or is encoded by DNA sequences that hybridize with the DNA sequences SEQ ID NO. 1, 3, 5, or fragments of these DNA sequences, in the region of DNA encoding the mature protein; or c) is encoded by DNA sequences that would hybridize without degeneracy of the genetic code, with the sequences defined in b), and which encode a polypeptide with a corresponding amino acid sequence.

12. Protein according to any of the preceding claims, characterized in that comprises the amino acid sequences SEQ ID NO: 2, 4 or 6.

13. Process for determining the enzymatic activity of the gcpE protein, characterized in that the phosphorylation of a sugar or a phosphorous sugar, or of a biosynthesis precursor is detected. of isoprenoid, in particular the phosphorylation of 2-C-methyl-D-erythritol, 2-C-methyl-D-erythritol phosphate, in particular 2-C-methyl-D-erythritol 4-phosphate, 2-C- methyl-D-erythrose, 2-C-methyl-D-erythrose phosphate, in particular 2-C-methyl-D-erythrose 4-phosphate, and phosphate and alcohol precursors.

14. Process according to claim 13, further characterized in that the phosphorylation of the following phosphates and alcohols is detected: CH2 (OH) -C (CH3) = C (OH) -CH2-O-PO (OH) 2, CH2 (OH) -C (CH3) = C (OH) -CH2-OH, CH2 (OH) -CH (CH3) -CO-CH2-O-PO (OH) 2, CH2 (OH) -CH (CH3) -CO-CH2OH CH2 = C (CH3) -CO-CH2-O-PO (OH) 2, CH_ = C (CH3) -CO-CH2-OH, CH2 = C (CH3) -CH (OH) -CH2-O-PO ( OH) 2, CH2 = C (CH3) -CH (OH) -CH2-OH, CH2 (OH) -C (= CH2) -C (OH) -CH2-0-PO (OH) 2, CH2 (OH) -C (= CH2) -C (OH) -CH2-OH, CHO-CH (CH3) -CH (OH) -CH2-O-PO- (OH) 2, CHO-CH (CH3) -CH (OH) -CH2-OH, CH2 (OH) -C (OH) (CH3 ) -CH = CH-O-PO (OH) 2, CH2 (OH) -C (OH) (CH3) -CH = CH-OH, CH (OH) = C (CH3) -CH (OH) -CH2- O-PO (OH) 2, CH (OH) = C (CH3) -CH (OH) -CH2-OH, (CH3) 2HC-CO-CH2-O-PO (OH) 2, (CH3) 2HC-CO -CH2-OH, (CH3) 2HC-CH (OH) -CH2-O-PO (OH) 2, (CH3) 2HC-CH (OH) -CH2-OH.

15. - Process for the combined determination of the enzymatic activity of DOXP-synthase and DOXP-reductase, characterized in that the conversion of glyceraldehyde 3-phosphate to 4-phosphate of 2-C-methyleritritol is detected.

16. Process for selecting a compound for the treatment of infectious processes in humans and animals, characterized in that it comprises: a) providing a host cell containing a recombinant expression vector, wherein the vector comprises at least a portion of the sequence of oligonucleotides according to SEQ ID NO: 1, SEQ ID NO: 3 or SEQ ID NO: 5, or their variants or analogs thereof; and in addition, a compound that is suspected to have antifungal, antibiotic, antiparasitic or antiviral action, in humans and animals; b) bringing the host cell into contact with the compound; and c) determining the antimicrobial, antifungal, antibiotic, antiparasitic or antiviral action of the compound.

17. Process for selecting compounds for treating plants, characterized said process because it comprises: a) providing a host cell containing a recombinant expression vector, wherein the vector comprises at least a portion of the oligonucleotide sequence according to SEQ ID NO: 1, SEQ ID NO: 3 OR SEQ ID NO: 5, or its variants or its analogues; and in addition, a compound that is suspected to have antimicrobial, antiviral, antiparasitic, bactericidal, fungicidal, or herbicidal action in plants; b) bringing the host cell into contact with the compound; and c) determining the antimicrobial, antiviral, antiparasitic, fungicidal or herbicidal action of the compound.

18. The use of the DNA according to any of claims 1 to 5, or of the proteins according to any of claims 9 to 12, or of transgenic systems according to claim 7, for the prevention or treatment of diseases in humans and animals.