Document Detail

A conserved amphipathic ligand binding region influences k-path-dependent activity of cytochrome C oxidase.
MedLine Citation:
PMID:  23351100     Owner:  NLM     Status:  MEDLINE    
A conserved, crystallographically defined bile acid binding site was originally identified in the membrane domain of mammalian and bacterial cytochrome c oxidase (CcO). Current studies show other amphipathic molecules including detergents, fatty acids, steroids, and porphyrins bind to this site and affect the already 50% inhibited activity of the E101A mutant of Rhodobacter sphaeroides CcO as well as altering the activity of wild-type and bovine enzymes. Dodecyl maltoside, Triton X100, C12E8, lysophophatidylcholine, and CHOBIMALT detergents further inhibit RsCcO E101A, with lesser inhibition observed in wild-type. The detergent inhibition is overcome in the presence of micromolar concentrations of steroids and porphyrin analogues including deoxycholate, cholesteryl hemisuccinate, bilirubin, and protoporphyrin IX. In addition to alleviating detergent inhibition, amphipathic carboxylates including arachidonic, docosahexanoic, and phytanic acids stimulate the activity of E101A to wild-type levels by providing the missing carboxyl group. Computational modeling of dodecyl maltoside, bilirubin, and protoporphyrin IX into the conserved steroid site shows energetically favorable binding modes for these ligands and suggests that a groove at the interface of subunit I and II, including the entrance to the K-path and helix VIII of subunit I, mediates the observed competitive ligand interactions involving two overlapping sites. Spectral analysis indicates that ligand binding to this region affects CcO activity by altering the K-path-dependent electron transfer equilibrium between heme a and heme a(3). The high affinity and specificity of a number of compounds for this region, and its conservation and impact on CcO activity, support its physiological significance.
Carrie Hiser; Leann Buhrow; Jian Liu; Leslie Kuhn; Shelagh Ferguson-Miller
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-02-12
Journal Detail:
Title:  Biochemistry     Volume:  52     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-27     Completed Date:  2013-04-15     Revised Date:  2014-02-27    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1385-96     Citation Subset:  IM    
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MeSH Terms
Bile Acids and Salts / metabolism
Bilirubin / metabolism
Binding Sites
Deoxycholic Acid / metabolism
Detergents / metabolism
Electron Transport Complex IV / chemistry*,  genetics,  metabolism*
Maltose / analogs & derivatives,  metabolism
Molecular Docking Simulation
Point Mutation
Protein Binding
Protein Structure, Secondary
Protein Subunits / chemistry,  genetics,  metabolism
Protoporphyrins / metabolism
Rhodobacter sphaeroides / enzymology*,  genetics,  metabolism
Substrate Specificity
Grant Support
Reg. No./Substance:
0/Bile Acids and Salts; 0/Detergents; 0/Protein Subunits; 0/Protoporphyrins; 0/dodecyl maltopyranoside; 005990WHZZ/Deoxycholic Acid; 553-12-8/protoporphyrin IX; 69-79-4/Maltose; EC Transport Complex IV; RFM9X3LJ49/Bilirubin

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

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