Document Detail


Mechanism of binding of NO to soluble guanylyl cyclase: implication for the second NO binding to the heme proximal site.
MedLine Citation:
PMID:  22401134     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Soluble guanylyl cyclase (sGC), the key enzyme for the formation of second messenger cyclic GMP, is an authentic sensor for nitric oxide (NO). Binding of NO to sGC leads to strong activation of the enzyme activity. Multiple molecules and steps of binding of NO to sGC have been implicated, but the target of the second NO and the detailed binding mechanism remain controversial. In this study, we used (15)NO and (14)NO and anaerobic sequential mixing-freeze-quench electron paramagnetic resonance to unambiguously confirm that the heme Fe is the target of the second NO. The linear dependence on NO concentration up to 600 s(-1) for the observed rate of the second step of NO binding not only indicates that the binding site of the second NO is different from that in the first step, i.e., the proximal site of the heme, but also supports a concerted mechanism in which the dissociation of the His105 proximal ligand occurs simultaneously with the binding of the second NO molecule. Computer modeling successfully predicts the kinetics of formation of a set of five-coordinate NO complexes with the ligand on either the distal or proximal site and supports the selective release of NO from the distal side of the transient bis-NO-sGC complex. Thus, as has been demonstrated with cytochrome c', a five-coordinate NO-sGC complex containing a proximal NO is formed after the binding of the second NO.
Authors:
Emil Martin; Vladimir Berka; Iraida Sharina; Ah-Lim Tsai
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-19
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-03     Completed Date:  2012-05-21     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2737-46     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Internal Medicine, The University of Texas Medical School at Houston, Houston, Texas 77030, United States. emil.martin@uth.tmc.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Cell Line
Computer Simulation
Electron Spin Resonance Spectroscopy
Enzyme Activation
Guanylate Cyclase / metabolism*
Heme / metabolism*
Kinetics
Nitric Oxide / metabolism*
Receptors, Cytoplasmic and Nuclear / metabolism*
Spodoptera
Grant Support
ID/Acronym/Agency:
HL088128/HL/NHLBI NIH HHS; HL095820/HL/NHLBI NIH HHS; R01 HL088128/HL/NHLBI NIH HHS; R01 HL095820/HL/NHLBI NIH HHS; R01 HL095820-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Cytoplasmic and Nuclear; 10102-43-9/Nitric Oxide; 14875-96-8/Heme; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/soluble guanylyl cyclase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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