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Allosteric Inhibition of Adenylyl Cyclase Type 5 by G-Protein: A Molecular Dynamics Study

1
CiTCoM, CNRS, Université de Paris, F-75006 Paris, France
2
CNRS, UMR 5086 Molecular Microbiology and Structural Biochemistry, University of Lyon, F-69367 Lyon, France
*
Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(9), 1330; https://doi.org/10.3390/biom10091330
Received: 10 July 2020 / Revised: 15 September 2020 / Accepted: 16 September 2020 / Published: 17 September 2020
(This article belongs to the Section Molecular Structure and Dynamics)
Adenylyl cyclases (ACs) have a crucial role in many signal transduction pathways, in particular in the intricate control of cyclic AMP (cAMP) generation from adenosine triphosphate (ATP). Using homology models developed from existing structural data and docking experiments, we have carried out all-atom, microsecond-scale molecular dynamics simulations on the AC5 isoform of adenylyl cyclase bound to the inhibitory G-protein subunit Gαi in the presence and in the absence of ATP. The results show that Gαi has significant effects on the structure and flexibility of adenylyl cyclase, as observed earlier for the binding of ATP and Gsα. New data on Gαi bound to the C1 domain of AC5 help explain how Gαi inhibits enzyme activity and obtain insight on its regulation. Simulations also suggest a crucial role of ATP in the regulation of the stimulation and inhibition of AC5. View Full-Text
Keywords: molecular dynamics; flexibility; protein-protein interactions; allostery; enzyme activity; docking; homology models molecular dynamics; flexibility; protein-protein interactions; allostery; enzyme activity; docking; homology models
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MDPI and ACS Style

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

AMA Style

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 Style

Frezza, Elisa; Amans, Tina-Méryl; Martin, Juliette. 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

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