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Structures of cGMP-Dependent Protein Kinase (PKG) I? Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability.

ABSTRACT: cGMP-dependent protein kinase (PKG) I? is a central regulator of smooth muscle tone and vasorelaxation. The N-terminal leucine zipper (LZ) domain dimerizes and targets PKG I? by interacting with G-kinase-anchoring proteins. The PKG I? LZ contains C42 that is known to form a disulfide bond upon oxidation and to activate PKG I?. To understand the molecular details of the PKG I? LZ and C42-C42' disulfide bond, we determined crystal structures of the PKG I? wild-type (WT) LZ and C42L LZ. Our data demonstrate that the C42-C42' disulfide bond dramatically stabilizes PKG I? and that the C42L mutant mimics the oxidized WT LZ structurally.

SUBMITTER: Qin L

PROVIDER: S-EPMC4838416 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability.

Qin Liying L Reger Albert S AS Guo Elaine E Yang Matthew P MP Zwart Peter P Casteel Darren E DE Kim Choel C

Biochemistry 20150715 29

cGMP-dependent protein kinase (PKG) Iα is a central regulator of smooth muscle tone and vasorelaxation. The N-terminal leucine zipper (LZ) domain dimerizes and targets PKG Iα by interacting with G-kinase-anchoring proteins. The PKG Iα LZ contains C42 that is known to form a disulfide bond upon oxidation and to activate PKG Iα. To understand the molecular details of the PKG Iα LZ and C42-C42' disulfide bond, we determined crystal structures of the PKG Iα wild-type (WT) LZ and C42L LZ. Our data de ...[more]

PMID: 26132214

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