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

Biochemistry. 2015 Jul 28;54(29):4419-22. doi: 10.1021/acs.biochem.5b00572. Epub 2015 Jul 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain
  • Crystallography, X-Ray
  • Cyclic GMP-Dependent Protein Kinase Type I / chemistry*
  • Cystine / chemistry*
  • Enzyme Stability
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Quaternary
  • Transition Temperature

Substances

  • Cystine
  • Cyclic GMP-Dependent Protein Kinase Type I
  • PRKG1 protein, human

Associated data

  • PDB/4R4L