Document Detail


A novel insight into the heme and NO/CO binding mechanism of the alpha subunit of human soluble guanylate cyclase.
MedLine Citation:
PMID:  21725643     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Human soluble guanylate cyclase (sGC), a critical heme-containing enzyme in the NO-signaling pathway of eukaryotes, is an αβ heterodimeric hemoprotein. Upon the binding of NO to the heme, sGC catalyzes the conversion of GTP to cyclic GMP, playing a crucial role in many physiological processes. However, the specific contribution of the α and β subunits of sGC in the intact heme binding remained intangible. The recombinant human sGC α1 subunit has been expressed in Escherichia coli and characterized for the first time. The heme binding and related NO/CO binding properties of both the α1 subunit and the β1 subunit were investigated via heme reconstitution, UV-vis spectroscopy, EPR spectroscopy, stopped-flow kinetics, and homology modeling. These results indicated that the α1 subunit of human sGC, lacking the conserved axial ligand, is likely to interact with heme noncovalently. On the basis of the equilibrium and kinetics of CO binding to sGC, one possible CO binding model was proposed. CO binds to human sGCβ195 by simple one-step binding, whereas CO binds to human sGCα259, possibly from both axial positions through a more complex process. The kinetics of NO dissociation from human sGC indicated that the NO dissociation from sGC was complex, with at least two release phases, and human sGCα259 has a smaller k (1) but a larger k (2). Additionally, the role of the cavity of the α1 subunit of human sGC was explored, and the results indicate that the cavity likely accommodates heme. These results are beneficial for understanding the overall structure of the heme binding site of the human sGC and the NO/CO signaling mechanism.
Authors:
Fangfang Zhong; Jie Pan; Xiaoxiao Liu; Hongyan Wang; Tianlei Ying; Jihu Su; Zhong-Xian Huang; Xiangshi Tan
Related Documents :
2148683 - Nucleotide regulation of escherichia coli glycerol kinase: initial-velocity and substra...
9309223 - Binding of allosteric effectors to ribonucleotide reductase protein r1: reduction of ac...
1311683 - Characterization of hepatocyte-growth-factor receptors on meth a cells.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-2
Journal Detail:
Title:  Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry     Volume:  -     ISSN:  1432-1327     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9616326     Medline TA:  J Biol Inorg Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Chemistry, Fudan University, Shanghai, 200433, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Non steroidal anti-inflammatory drugs modulate the physicochemical properties of plasma membrane in ...
Next Document:  A case of lymphoplasmacyte-rich meningioma of the jugular foramen.