title: Structures of cGMP-Dependent Protein Kinase (PKG) Iα Leucine Zippers Reveal an Interchain Disulfide Bond Important for Dimer Stability.
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.
authors.forename: Liying
authors.initials: L
authors.lastname: Qin
authors.forename: Albert S
authors.initials: AS
authors.lastname: Reger
authors.forename: Elaine
authors.initials: E
authors.lastname: Guo
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Yang
authors.affiliation: ⊥Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Zwart
authors.affiliation: @Department of Medicine, University of California at San Diego, La Jolla, California 92093, United States.
authors.forename: Darren E
authors.initials: DE
authors.lastname: Casteel
authors.forename: Choel
authors.initials: C
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D062965:Cyclic GMP-Dependent Protein Kinase Type I / Q000737:chemistry*; D003553:Cystine / Q000737:chemistry*; D004795:Enzyme Stability; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D044366:Transition Temperature
chemical_list: D003553:Cystine; D062965:Cyclic GMP-Dependent Protein Kinase Type I; C569718:PRKG1 protein, human