RGD Reference Report - Dissociation of nitric oxide from soluble guanylate cyclase and heme-nitric oxide/oxygen binding domain constructs. - Rat Genome Database

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Dissociation of nitric oxide from soluble guanylate cyclase and heme-nitric oxide/oxygen binding domain constructs.

Authors: Winger, JA  Derbyshire, ER  Marletta, MA 
Citation: Winger JA, etal., J Biol Chem. 2007 Jan 12;282(2):897-907. Epub 2006 Nov 10.
RGD ID: 1641948
Pubmed: PMID:17098738   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M606327200   (Journal Full-text)

Regulation of soluble guanylate cyclase (sGC), the primary NO receptor, is linked to NO binding to the prosthetic heme group. Recent studies have demonstrated that the degree and duration of sGC activation depend on the presence and ratio of purine nucleotides and on the presence of excess NO. We measured NO dissociation from full-length alpha1beta1 sGC, and the constructs beta1(1-194), beta1(1-385), and beta2(1-217), at 37 and 10 degrees C with and without the substrate analogue guanosine-5'-[(alpha,beta-methylene]triphosphate (GMPCPP) or the activator 3-(5'-hydroxymethyl-3'-furyl)-1-benzylindazole (YC-1). NO dissociation from each construct was complex, requiring two exponentials to fit the data. Decreasing the temperature decreased the contribution of the faster exponential for all constructs. Inclusion of YC-1 moderately accelerated NO dissociation from sGC and beta2(1-217) at 37 degrees C and dramatically accelerated NO dissociation from sGC at 10 degrees C. The presence of GMPCPP also dramatically accelerated NO dissociation from sGC at 10 degrees C. This acceleration is due to increases in the observed rate for each exponential and in the contribution of the faster exponential. Increases in the contribution of the faster exponential correlated with higher activation of sGC by NO. These data indicate that the sGC ferrous-nitrosyl complex adopts two 5-coordinate conformations, a lower activity "closed" form, which releases NO slowly, and a higher activity "open" form, which releases NO rapidly. The ratio of these two species affects the overall rate of NO dissociation. These results have implications for the function of sGC in vivo, where there is evidence for two NO-regulated activity states.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gucy1a1Ratguanylate cyclase complex, soluble  IDA  RGD 
Gucy1b1Ratguanylate cyclase complex, soluble  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Gucy1a1Ratnitric oxide binding  IDA  RGD 
Gucy1b1Ratnitric oxide binding  IDA  RGD 
Gucy1b2Ratnitric oxide binding  IDA  RGD 
Gucy1a1Ratprotein-containing complex binding  IDA heterodimerizationRGD 
Gucy1b1Ratprotein-containing complex binding  IDA heterodimerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gucy1a1  (guanylate cyclase 1 soluble subunit alpha 1)
Gucy1b1  (guanylate cyclase 1 soluble subunit beta 1)
Gucy1b2  (guanylate cyclase 1 soluble subunit beta 2)


Additional Information