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G?i1 inhibition mechanism of ATP-bound adenylyl cyclase type 5.

ABSTRACT: 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?i, and stimulatory, G?s subunits. In the past twenty years, several crystal structures of AC in isolated form and complexed to G?s subunits have been resolved. Nevertheless, the molecular basis of the inhibition mechanism of AC, induced by G?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?i have been analyzed to investigate the conformational impact of G?i association on ATP-bound AC5. The results show that G?i appears to inhibit the activity of AC5 by preventing the formation of a reactive ATP conformation.

SUBMITTER: Narzi D

PROVIDER: S-EPMC7833170 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Gαi1 inhibition mechanism of ATP-bound adenylyl cyclase type 5.

Narzi Daniele D van Keulen Siri C SC Röthlisberger Ursula U

PloS one 20210125 1

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, Gαi, and stimulatory, Gαs subunits. In the past twenty years, several crystal structures of AC in isolated form and complexed to Gαs subunits have been resolved. N ...[more]

PMID: 33493164

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