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Nucleotide regulation of soluble guanylate cyclase substrate specificity
- Source :
- Biochemistry. 48(31)
- Publication Year :
- 2009
-
Abstract
- Soluble guanylate cyclase (sGC) serves as a receptor for the signaling agent nitric oxide (NO). sGC synthesis of cGMP is regulated by NO, GTP, ATP, and allosteric activators such as YC-1. The guanylate cyclase activity and adenylate cyclase activity of full-length sGC and the sGC catalytic domain constructs (alpha1(cat)beta1(cat)) are reported here. ATP is a mixed-type inhibitor of cGMP production for both sGC and alpha1(cat)beta1(cat), indicating that the C-terminus of sGC contains an allosteric nucleotide binding site. YC-1 did not activate alpha1(cat)beta1(cat) or compete with ATP inhibition of cGMP synthesis, which suggests that YC-1 and ATP bind to distinct sites. alpha1(cat)beta1(cat) and NO-stimulated sGC also synthesize cAMP, but this activity is inhibited by ATP via noncompetitive substrate inhibition and by GTP via mixed-type inhibition. Additionally, the adenylate cyclase activity of purified sGC was inhibited by PC12 lysate, suggesting that an intracellular small molecule or protein regulates this activity in vivo.
- Subjects :
- inorganic chemicals
GUCY1B3
Protein Conformation
Allosteric regulation
Adenylate kinase
Receptors, Cytoplasmic and Nuclear
Biochemistry
PC12 Cells
Article
Substrate Specificity
Adenosine Triphosphate
Soluble Guanylyl Cyclase
Allosteric Regulation
Catalytic Domain
Animals
heterocyclic compounds
Chemistry
Guanylate cyclase activity
GUCY1A3
Guanylate cyclase 2C
Rats
Protein Subunits
Guanylate Cyclase
cardiovascular system
Guanosine Triphosphate
Soluble guanylyl cyclase
Cyclase activity
Allosteric Site
Adenylyl Cyclases
Subjects
Details
- ISSN :
- 15204995
- Volume :
- 48
- Issue :
- 31
- Database :
- OpenAIRE
- Journal :
- Biochemistry
- Accession number :
- edsair.doi.dedup.....1cb7e53ea9e1d6121f326fb692ddb966