Premium
Interaction between soluble guanylyl cyclase (sGC) and protein disulfide isomerase (PDI) in smooth muscle cells
Author(s) -
Heckler Erin,
Baskaran Padmamalini,
Beuve Annie
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb67
Subject(s) - soluble guanylyl cyclase , guanosine , chemistry , cysteine , biochemistry , enzyme , heme , cyclic guanosine monophosphate , protein disulfide isomerase , nitric oxide , guanosine triphosphate , cofactor , gtp' , gucy1b3 , gucy1a3 , thiol , glutathione , guanosine monophosphate , cytosol , cyclase , guanylate cyclase , guanylate cyclase 2c , nucleotide , organic chemistry , gene
Soluble guanylyl cyclase (sGC) is a nitric oxide (NO) sensor in the cardiovascular system. This heterodimeric enzyme contains a heme cofactor and converts guanosine triphosphate (GTP) to the signaling molecule, cyclic guanosine monophosphate (cGMP). Upon NO binding to the heme, production of cGMP is stimulated several hundred fold. We showed that sGC can be desensitized via S‐nitrosation (Sayed et al. PNAS 2007, 104, 12312‐17). More recently, Zheng et al implicate the reduction of key cysteine residues in sGC for enzyme activation (Zheng, et al. Cardiovascular Research published online Jan 19, 2011). This cytosolic enzyme has 34 cysteines, a thiol titer estimates that twelve of these are disulfide‐bonded, leaving a significant number of predicted free thiols in the native form of the enzyme. Previous work suggested that sGC associates with PDI (Balashova, et al. JBC 2005, 280, 2186‐2196; Sayed and Beuve unpublished observations). We show that this is a direct redox interaction involving key cysteines in sGC and PDI. The biological relevance of this interaction is under investigation. Supported by NIH Grant R01 GM067640