Allosteric Inhibition of Adenylyl Cyclase Type 5 by G-Protein: A Molecular Dynamics Study
<p>Structure of the cytoplasmic segment of the AC5 isoform of adenylyl cyclase and of its complexes with ATP and the regulating G-proteins Gsα and Gαi viewed from the side closest to the cell membrane. Proteins are shown as backbone ribbons. The C1 and C2 subunits of AC5 are colored blue and red respectively, Gsα is colored green, and Gαi is colored purple. ATP is shown in a CPK representation with standard chemical coloring. In each case, the structures are averages taken from the molecular dynamics simulations. For the AC5 in complex with Gαi with and without ATP, we chose one of the docking poses we used in this work.</p> "> Figure 2
<p>The two different configurations of the Gαi + AC5 + ATP complex simulated in this study. (<b>A</b>): Gαi_sym + AC5 + ATP: Gαi has an orientation symmetrical to the Gsα protein in the AC5 + Gsα complex. (<b>B</b>): Gαi_tilted + AC5 + ATP: Gαi protein is tilted with respect to AC5.</p> "> Figure 3
<p>Illustration of the key regions of AC5 catalytic domain structure with bound ATP. The C1 domain is colored blue and the C2 domain is in red, with relevant parts in darker color: the helices of C2 are involved in the binding of the stimulatory protein Gsα, the helices of C1 are involved in the binding of the inhibitory protein Gαi, the β2 loop of C2 (<b>left side</b>), and the β4 loop of C2 (<b>right side</b>), which bears the catalytic Lysine residue. The green oval indicates the binding site of Gsα, and the purple oval indicates the binding site of Gαi.</p> "> Figure 4
<p>Snapshots of the Gαi + AC5 + ATP complexes observed during the simulations, viewed from the membrane side. Gαi structures extracted every 250 ns are colored on a rainbow scale from blue to red. The C1 domain of AC5 is colored in gray and the C2 domain in beige.</p> "> Figure 5
<p>Substates of domain C2 observed during the simulation of Gαi_sym + AC5 + ATP complex. Left side: Root mean square deviation (RMSD) time series for the C2 domain, colored according to cluster membership. Right: structures closest to the center of each cluster, and relative size of each cluster as percentages. Prominent structural changes are indicated by red arrows.</p> "> Figure 6
<p>Changes in conformation induced by Gαi protein. (<b>A</b>) scenario where ATP is already bound to AC5 when Gαi interacts, (<b>B</b>) scenario where ATP is not yet bound to AC5 when Gαi interacts. More intense colors (blue for domain C1 and red for domain C2) correspond to larger movements compared to the preceding structure (i.e., AC5 + ATP for A and AC5 and AC5 + Gαi for B) on a scale of 0 to 4 Å. The insets display the β4 loop.</p> "> Figure 7
<p>Changes in flexibility induced by G proteins. (<b>A</b>) Scenario where ATP is already bound to AC5 when Gαi interacts, (<b>B</b>) scenario where ATP is not yet bound to AC5 when Gαi interacts. More intense colors (orange for increased flexibility and cyan for decreased flexibility) correspond to differences with respect to the preceding structure on a scale of −1.2 to +1.2 Å. The insets display the β4 loop.</p> "> Figure 8
<p>Interactions between ATP and key residues in different complexes. (<b>A</b>) active AC5 + ATP + Gsα, (<b>B</b>) inactive AC5 + ATP complex, (<b>C)</b> inactive Gαi_tilted + AC5 + ATP complex. Key residues of C2 are shown as sticks and colored in purple (LYS 1065) and green (ARG 1029). The C1 and C2 subunits of AC5 are colored blue and red, respectively. For clarity, the region 394–428 of C1 is omitted from the representation.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Models
2.2. All-Atom Molecular Dynamics Simulations
2.3. Analysis of All-Atom Molecular Dynamics Simulations
3. Results
3.1. Overview of Simulations
3.2. Stability of Gαi + AC5 Complexes in the Presence and in the Absence of ATP
3.3. Impact of Gαi on AC5 + ATP
3.4. Impact of Gαi on Apo AC5 and Further Impact of ATP on AC5 + Gαi
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Hanson, M.A.; Stevens, R.C. Discovery of New GPCR Biology: One Receptor Structure at a Time. Structure 2009, 17, 8–14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hardman, J.G.; Robison, G.A.; Sutherland, E.W. Cyclic Nucleotides. Annu. Rev. Physiol. 1971, 33, 311–336. [Google Scholar] [CrossRef] [PubMed]
- Andersson, R.; Nilsson, K. Cyclic AMP and Calcium in Relaxation in Intestinal Smooth Muscle. Nat. New Biol. 1972, 238, 119–120. [Google Scholar] [CrossRef] [PubMed]
- DeMaria, S.; Ngai, J. The cell biology of smell. J. Cell Biol. 2010, 191, 443–452. [Google Scholar] [CrossRef] [PubMed]
- Davis, R.L.; Cherry, J.; Dauwalder, B.; Han, P.-L.; Skoulakis, E.M.C. The cyclic AMP system andDrosophila learning. In Signal Transduction Mechanisms; Springer: Berlin, Germany, 1995; pp. 271–278. [Google Scholar]
- Kandel, E.R. The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses. Science 2001, 294, 1030–1038. [Google Scholar] [CrossRef] [Green Version]
- Wu, Z.L.; Thomas, S.A.; Villacres, E.C.; Xia, Z.; Simmons, M.L.; Chavkin, C.; Palmiter, R.D.; Storm, D.R. Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice. Proc. Natl. Acad. Sci. USA 1995, 92, 220–224. [Google Scholar] [CrossRef] [Green Version]
- Kamenetsky, M.; Middelhaufe, S.; Bank, E.M.; Levin, L.R.; Buck, J.; Steegborn, C. Molecular Details of cAMP Generation in Mammalian Cells: A Tale of Two Systems. J. Mol. Biol. 2006, 362, 623–639. [Google Scholar] [CrossRef] [Green Version]
- Sunahara, R.K.; Dessauer, C.W.; Gilman, A.G. Complexity and Diversity of Mammalian Adenylyl Cyclases. Annu. Rev. Pharmacol. Toxicol. 1996, 36, 461–480. [Google Scholar] [CrossRef]
- Sunahara, R.K. Isoforms of Mammalian Adenylyl Cyclase: Multiplicities of Signaling. Mol. Interv. 2002, 2, 168–184. [Google Scholar] [CrossRef] [Green Version]
- Krupinski, J.; Coussen, F.; Bakalyar, H.; Tang, W.; Feinstein, P.; Orth, K.; Slaughter, C.; Reed, R.; Gilman, A. Adenylyl cyclase amino acid sequence: Possible channel- or transporter-like structure. Science 1989, 244, 1558–1564. [Google Scholar] [CrossRef]
- Tang, W.-J.; Gilman, A.G. Adenylyl cyclases. Cell 1992, 70, 869–872. [Google Scholar] [CrossRef]
- Tesmer, J.J.; Sunahara, R.K.; Johnson, R.A.; Gosselin, G.; Gilman, A.G.; Sprang, S.R. Two-Metal-Ion Catalysis in Adenylyl Cyclase. Science 1999, 285, 756–760. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jacobowitz, O.; Chen, J.; Premont, R.T.; Iyengar, R. Stimulation of specific types of Gs-stimulated adenylyl cyclases by phorbol ester treatment. J. Biol. Chem. 1993, 268, 3829–3832. [Google Scholar]
- Gilman, A.G. G proteins and regulation of adenylyl cyclase. Biosci. Rep. 1995, 15, 65–97. [Google Scholar] [CrossRef] [PubMed]
- Rasmussen, S.G.F.; DeVree, B.T.; Zou, Y.; Kruse, A.C.; Chung, K.Y.; Kobilka, T.S.; Thian, F.S.; Chae, P.S.; Pardon, E.; Calinski, D.; et al. Crystal structure of the β2 adrenergic receptor—Gs protein complex. Nature 2011, 477, 549–555. [Google Scholar] [CrossRef] [Green Version]
- Nygaard, R.; Zou, Y.; Dror, R.O.; Mildorf, T.J.; Arlow, D.H.; Manglik, A.; Pan, A.C.; Liu, C.W.; Fung, J.J.; Bokoch, M.P.; et al. The dynamic process of β(2)—Adrenergic receptor activation. Cell 2013, 152, 532–542. [Google Scholar] [CrossRef] [Green Version]
- Patel, T.B.; Du, Z.; Pierre, S.; Cartin, L.; Scholich, K. Molecular biological approaches to unravel adenylyl cyclase signaling and function. Gene 2001, 269, 13–25. [Google Scholar] [CrossRef]
- Sadana, R.; Dessauer, C.W. Physiological roles for G protein-regulated adenylyl cyclase isoforms: Insights from knockout and overexpression studies. Neurosignals 2008, 17, 5–22. [Google Scholar] [CrossRef]
- Wang, S.-C.; Lin, J.-T.; Chern, Y. Novel Regulation of Adenylyl Cyclases by Direct Protein-Protein Interactions: Insights from Snapin and Ric8a. Neurosignals 2009, 17, 169–180. [Google Scholar] [CrossRef]
- Zhang, G.; Liu, Y.; Ruoho, A.E.; Hurley, J.H. Structure of the adenylyl cyclase catalytic core. Nature 1997, 386, 247–253. [Google Scholar] [CrossRef]
- Perreault, M.L.; Hasbi, A.; O’Dowd, B.F.; George, S.R. The Dopamine D1–D2 Receptor Heteromer in Striatal Medium Spiny Neurons: Evidence for a Third Distinct Neuronal Pathway in Basal Ganglia. Front. Neuroanat. 2011, 5, 31. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tesmer, J.J.G.; Sunahara, R.K.; Gilman, A.G.; Sprang, S.R. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsα·GTPγS. Science 1997, 278, 1907–1916. [Google Scholar] [CrossRef] [PubMed]
- Dessauer, C.W.; Tesmer, J.J.; Sprang, S.R.; Gilman, A.G. Identification of a Gi Binding Site on Type V Adenylyl Cyclase. J. Biol. Chem. 1998, 273, 25831–25839. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Frezza, E.; Martin, J.; Lavery, R. A molecular dynamics study of adenylyl cyclase: The impact of ATP and G-protein binding. PLoS ONE 2018, 13, e0196207. [Google Scholar] [CrossRef] [Green Version]
- Ho, D.; Yan, L.; Iwatsubo, K.; Vatner, D.E.; Vatner, S.F. Modulation of β-adrenergic receptor signaling in heart failure and longevity: Targeting adenylyl cyclase type 5. Heart Fail. Rev. 2010, 15, 495–512. [Google Scholar] [CrossRef] [Green Version]
- Vatner, S.F.; Park, M.; Yan, L.; Lee, G.J.; Lai, L.P.; Iwatsubo, K.; Ishikawa, Y.; Pessin, J.; Vatner, D.E. Adenylyl cyclase type 5 in cardiac disease, metabolism, and aging. Am. J. Physiol. Circ. Physiol. 2013, 305, H1–H8. [Google Scholar] [CrossRef] [Green Version]
- Van Keulen, S.C.; Rothlisberger, U. Exploring the inhibition mechanism of adenylyl cyclase type 5 by n-terminal myristoylated Gαi1. PLoS Comput. Biol. 2017, 13, e1005673. [Google Scholar] [CrossRef]
- Van Keulen, S.C.; Narzi, D.; Rothlisberger, U. Association of Both Inhibitory and Stimulatory Gα Subunits Implies Adenylyl Cyclase 5 Deactivation. Biochemistry 2019, 58, 4317–4324. [Google Scholar] [CrossRef]
- Bruce, N.J.; Narzi, D.; Trpevski, D.; Van Keulen, S.C.; Nair, A.G.; Rothlisberger, U.; Wade, R.C.; Carloni, P.; Kotaleski, J.H. Regulation of adenylyl cyclase 5 in striatal neurons confers the ability to detect coincident neuromodulatory signals. PLoS Comput. Biol. 2019, 15, e1007382. [Google Scholar] [CrossRef] [Green Version]
- Steegborn, C. Structure, mechanism, and regulation of soluble adenylyl cyclases—Similarities and differences to transmembrane adenylyl cyclases. Biochim. Biophys. Acta 2014, 1842, 2535–2547. [Google Scholar] [CrossRef] [Green Version]
- Hurley, J.H. Structure, mechanism, and regulation of mammalian adenylyl cyclase. J. Biol. Chem. 1999, 274, 7599–7602. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fiser, A.; Sali, A. Modeller: Generation and Refinement of Homology-Based Protein Structure Models. Enzym. Eng. Evol. Gen. Methods 2003, 374, 461–491. [Google Scholar] [CrossRef]
- Shen, M.-Y.; Sali, A. Statistical potential for assessment and prediction of protein structures. Protein Sci. 2006, 15, 2507–2524. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Raw, A.S.; Coleman, D.E.; Gilman, A.G.; Sprang, S.R. Structural and Biochemical Characterization of the GTPγS-, GDP·Pi-, and GDP-Bound Forms of a GTPase-Deficient Gly42 → Val Mutant of Giα1. Biochemistry 1997, 36, 15660–15669. [Google Scholar] [CrossRef] [PubMed]
- Tesmer, J.J.; Berman, D.M.; Gilman, A.G.; Sprang, S.R. Structure of RGS4 Bound to AlF4−-Activated Giα1: Stabilization of the Transition State for GTP Hydrolysis. Cell 1997, 89, 251–261. [Google Scholar] [CrossRef] [Green Version]
- Van Keulen, S.C.; Rothlisberger, U. Effect of N-Terminal Myristoylation on the Active Conformation of Gαi1–GTP. Biochemistry 2016, 56, 271–280. [Google Scholar] [CrossRef] [Green Version]
- Kozakov, D.; Beglov, D.; Bohnuud, T.; Mottarella, S.E.; Xia, B.; Hall, D.R.; Vajda, S. How good is automated protein docking? Proteins Struct. Funct. Bioinform. 2013, 81, 2159–2166. [Google Scholar] [CrossRef] [Green Version]
- Vajda, S.; Yueh, C.; Beglov, D.; Bohnuud, T.; Mottarella, S.E.; Xia, B.; Hall, D.R.; Kozakov, D. New additions to the ClusPro server motivated by CAPRI. Proteins Struct. Funct. Bioinform. 2017, 85, 435–444. [Google Scholar] [CrossRef] [Green Version]
- Kozakov, D.; Hall, D.R.; Xia, B.; Porter, K.A.; Padhorny, D.; Yueh, C.; Beglov, D.; Vajda, S. The ClusPro web server for protein–protein docking. Nat. Protoc. 2017, 12, 255–278. [Google Scholar] [CrossRef]
- Qi, C.; Sorrentino, S.; Medalia, O.; Korkhov, V. The structure of a membrane adenylyl cyclase bound to an activated stimulatory G protein. Science 2019, 364, 389–394. [Google Scholar] [CrossRef]
- Berendsen, H.; Van Der Spoel, D.; Van Drunen, R. GROMACS: A message-passing parallel molecular dynamics implementation. Comput. Phys. Commun. 1995, 91, 43–56. [Google Scholar] [CrossRef]
- Lindahl, E.; Hess, B.; Van Der Spoel, D. GROMACS 3.0: A package for molecular simulation and trajectory analysis. Mol. Model. Annu. 2001, 7, 306–317. [Google Scholar] [CrossRef]
- Van Der Spoel, D.; Lindahl, E.; Hess, B.; Groenhof, G.; Mark, A.E.; Berendsen, H.J.C. GROMACS: Fast, flexible, and free. J. Comput. Chem. 2005, 26, 1701–1718. [Google Scholar] [CrossRef]
- Hess, B.; Kutzner, C.; Van Der Spoel, D.; Lindahl, E. GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. J. Chem. Theory Comput. 2008, 4, 435–447. [Google Scholar] [CrossRef] [Green Version]
- Pronk, S.; Páll, S.; Schulz, R.; Larsson, P.; Bjelkmar, P.; Apostolov, R.; Shirts, M.R.; Smith, J.C.; Kasson, P.M.; Van Der Spoel, D.; et al. GROMACS 4.5: A high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 2013, 29, 845–854. [Google Scholar] [CrossRef]
- Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J.L.; Dror, R.O.; Shaw, D.E. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins Struct. Funct. Bioinform. 2010, 78, 1950–1958. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Cieplak, P.; Kollman, P.A. How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J. Comput. Chem. 2000, 21, 1049–1074. [Google Scholar] [CrossRef]
- Hornak, V.; Abel, R.; Okur, A.; Strockbine, B.; Roitberg, A.; Simmerling, C.L. Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins Struct. Funct. Bioinform. 2006, 65, 712–725. [Google Scholar] [CrossRef] [Green Version]
- Lindorff-Larsen, K.; Maragakis, P.; Piana, S.; Eastwood, M.P.; Dror, R.O.; Shaw, D.E. Systematic Validation of Protein Force Fields against Experimental Data. PLoS ONE 2012, 7, e32131. [Google Scholar] [CrossRef] [Green Version]
- Dolinsky, T.J.; Nielsen, J.E.; McCammon, J.A.; Baker, N.A. PDB2PQR: An automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations. Nucleic Acids Res. 2004, 32, W665–W667. [Google Scholar] [CrossRef]
- Jorgensen, W.L.; Chandrasekhar, J.; Madura, J.D.; Impey, R.W.; Klein, M.L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926–935. [Google Scholar] [CrossRef]
- Dang, L.X. Mechanism and Thermodynamics of Ion Selectivity in Aqueous Solutions of 18-Crown-6 Ether: A Molecular Dynamics Study. J. Am. Chem. Soc. 1995, 117, 6954–6960. [Google Scholar] [CrossRef]
- Meagher, K.L.; Redman, L.T.; Carlson, H.A. Development of polyphosphate parameters for use with the AMBER force field. J. Comput. Chem. 2003, 24, 1016–1025. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allnér, O.; Nilsson, L.; Villa, A. Magnesium Ion–Water Coordination and Exchange in Biomolecular Simulations. J. Chem. Theory Comput. 2012, 8, 1493–1502. [Google Scholar] [CrossRef] [Green Version]
- Darden, T.; York, D.; Pedersen, L. Particle mesh Ewald: AnN⋅log (N) method for Ewald sums in large systems. J. Chem. Phys. 1993, 98, 10089–10092. [Google Scholar] [CrossRef] [Green Version]
- Essmann, U.; Perera, L.; Berkowitz, M.L.; Darden, T.; Lee, H.; Pedersen, L.G. A smooth particle mesh Ewald method. J. Chem. Phys. 1995, 103, 8577–8593. [Google Scholar] [CrossRef] [Green Version]
- Hess, B.; Bekker, H.; Berendsen, H.J.C.; Fraaije, J.G.E.M. LINCS: A linear constraint solver for molecular simulations. J. Comput. Chem 1997, 18, 1463–1472. [Google Scholar] [CrossRef]
- Berendsen, H.J.C.; Van Gunsteren, W.F.; Barnes, A.J. Molecular Liquids-Dynamics and Interactions. In Proceedings of the NATO Advanced Study Institute on Molecular Liquids, Dordretch, The Netherlands, 1 April 1984; pp. 475–500. [Google Scholar]
- Harvey, S.C.; Tan, R.K.Z.; Cheatham, T.E., III. The flying ice cube: Velocity rescaling in molecular dynamics leads to violation of energy equipartition. J. Comput. Chem. 1998, 19, 726–740. [Google Scholar] [CrossRef]
- Berendsen, H.J.C.; Postma, J.P.M.; Van Gunsteren, W.F.; DiNola, A.; Haak, J.R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984, 81, 3684–3690. [Google Scholar] [CrossRef] [Green Version]
- Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 2007, 126, 014101. [Google Scholar] [CrossRef] [Green Version]
- Parrinello, M. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys. 1981, 52, 7182. [Google Scholar] [CrossRef]
- Daura, X.; Gademann, K.; Jaun, B.; Seebach, D.; Van Gunsteren, W.F.; Mark, A.E. Peptide Folding: When Simulation Meets Experiment. Angew. Chem. Int. Ed. 1999, 38, 236–240. [Google Scholar] [CrossRef]
- Laskowski, R.A. SURFNET: A program for visualizing molecular surfaces, cavities, and intermolecular interactions. J. Mol. Graph. 1995, 13, 323–330. [Google Scholar] [CrossRef]
- Jones, S.; Thornton, J.M. Principles of protein-protein interactions. Proc. Natl. Acad. Sci. USA 1996, 93, 13–20. [Google Scholar] [CrossRef] [Green Version]
- Lee, B.; Richards, F. The interpretation of protein structures: Estimation of static accessibility. J. Mol. Biol. 1971, 55, 379–400. [Google Scholar] [CrossRef]
- Hahn, D.K.; Tusell, J.R.; Sprang, S.R.; Chu, X. Catalytic Mechanism of Mammalian Adenylyl Cyclase: A Computational Investigation. Biochemistry 2015, 54, 6252–6262. [Google Scholar] [CrossRef] [Green Version]
- R Development Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2011; ISBN 3-900051-07-0. Available online: http://www.R-project.org/ (accessed on 19 August 2011).
- Wickham, H. ggplot2: Elegant Graphics for Data Analysis; Springer: New York, NY, USA, 2016; ISBN 978-3-319-24277-4. [Google Scholar]
- Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera—A visualization system for exploratory research and analysis. J. Comput. Chem. 2004, 25, 1605–1612. [Google Scholar] [CrossRef] [Green Version]
- Frezza, E.; Martin, J.; Lavery, R. A molecular dynamics study of adenylyl cyclase: The impact of ATP and G-protein binding. Zenodo 2018. [Google Scholar] [CrossRef]
- Zhu, H.; Domingues, F.S.; Sommer, I.E.C.; Lengauer, T. NOXclass: Prediction of protein-protein interaction types. BMC Bioinform. 2006, 7, 27. [Google Scholar] [CrossRef] [Green Version]
- Lensink, M.F.; Velankar, S.; Wodak, S.J. Modeling protein-protein and protein-peptide complexes: CAPRI 6th edition. Proteins: Struct. Funct. Bioinform. 2016, 85, 359–377. [Google Scholar] [CrossRef]
- Lambright, D.G.; Noel, J.P.; Hamm, H.E.; Sigler, P.B. Structural determinants for activation of the α-subunit of a heterotrimeric G protein. Nature 1994, 369, 621–628. [Google Scholar] [CrossRef] [PubMed]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Frezza, E.; Amans, T.-M.; Martin, J. Allosteric Inhibition of Adenylyl Cyclase Type 5 by G-Protein: A Molecular Dynamics Study. Biomolecules 2020, 10, 1330. https://doi.org/10.3390/biom10091330
Frezza E, Amans T-M, Martin J. Allosteric Inhibition of Adenylyl Cyclase Type 5 by G-Protein: A Molecular Dynamics Study. Biomolecules. 2020; 10(9):1330. https://doi.org/10.3390/biom10091330
Chicago/Turabian StyleFrezza, Elisa, Tina-Méryl Amans, and Juliette Martin. 2020. "Allosteric Inhibition of Adenylyl Cyclase Type 5 by G-Protein: A Molecular Dynamics Study" Biomolecules 10, no. 9: 1330. https://doi.org/10.3390/biom10091330