Key result
Crystal structures of the PKG Iα wild-type and C42L leucine zippers demonstrate that the C42-C42' disulfide bond dramatically stabilizes PKG Iα and the C42L mutant structurally mimics the oxidized WT.
Structural insights into PKG Iα redox stabilization may guide targeted research; clinical relevance in cardiovascular disease remains untested.
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 demonstrate that the C42-C42' disulfide bond dramatically stabilizes PKG Iα and that the C42L mutant mimics the oxidized WT LZ structurally.
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Qin et al. (2015) studied this question. Crystal structures of the PKG Iα wild-type and C42L leucine zippers demonstrate that the C42-C42' disulfide bond dramatically stabilizes PKG Iα and the C42L mutant structurally mimics the oxidized WT.
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