Cyclic nucleotide selectivity of protein kinase G isozymes.

ABSTRACT: The intrinsic activity of the C-terminal catalytic (C) domain of cyclic guanosine monophosphate (cGMP)-dependent protein kinases (PKG) is inhibited by interactions with the N-terminal regulatory (R) domain. Selective binding of cGMP to cyclic nucleotide binding (CNB) domains within the R-domain disrupts the inhibitory R-C interaction, leading to the release and activation of the C-domain. Affinity measurements of mammalian and plasmodium PKG CNB domains reveal different degrees of cyclic nucleotide affinity and selectivity; the CNB domains adjacent to the C-domain are more cGMP selective and therefore critical for cGMP-dependent activation. Crystal structures of isolated CNB domains in the presence and absence of cyclic nucleotides reveal isozyme-specific contacts that explain cyclic nucle

SUBMITTER: Kim C 

PROVIDER: S-EPMC7784742 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature