G[alpha].sub.i1 inhibition mechanism of ATP-bound adenylyl cyclase type 5

Conversion of adenosine triphosphate (ATP) to the second messenger cyclic adenosine monophosphate (cAMP) is an essential reaction mechanism that takes place in eukaryotes, triggering a variety of signal transduction pathways. ATP conversion is catalyzed by the enzyme adenylyl cyclase (AC), which can...

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Bibliographic Details
Published in:PloS one 2021-01, Vol.16 (1), p.e0245197
Main Authors: Narzi, Daniele, van Keulen, Siri C, Röthlisberger, Ursula
Format: Article
Language:English
Subjects:
Adenosine triphosphate
Analysis
Cellular signal transduction
Chemical properties
Cyclic adenylic acid
Physiological aspects
Online Access:Get full text
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Summary:Conversion of adenosine triphosphate (ATP) to the second messenger cyclic adenosine monophosphate (cAMP) is an essential reaction mechanism that takes place in eukaryotes, triggering a variety of signal transduction pathways. ATP conversion is catalyzed by the enzyme adenylyl cyclase (AC), which can be regulated by binding inhibitory, G[alpha].sub.i, and stimulatory, G[alpha].sub.s subunits. In the past twenty years, several crystal structures of AC in isolated form and complexed to G[alpha].sub.s subunits have been resolved. Nevertheless, the molecular basis of the inhibition mechanism of AC, induced by G[alpha].sub.i, is still far from being fully understood. Here, classical molecular dynamics simulations of the isolated holo AC protein type 5 and the holo binary complex AC5:G[alpha].sub.i have been analyzed to investigate the conformational impact of G[alpha].sub.i association on ATP-bound AC5. The results show that G[alpha].sub.i appears to inhibit the activity of AC5 by preventing the formation of a reactive ATP conformation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0245197