Membrane potential-controlled inhibition of cytochrome c oxidase by zinc

Like many voltage-sensitive ion pumps, cytochrome c oxidase is inhibited by zinc. Binding of zinc to the outside surface of Rhodobacter sphaeroides cytochrome c oxidase inhibits the enzyme with a K(I) of < or = 5 microm when the enzyme is reconstituted into phospholipid vesicles in the presence o...

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Bibliographic Details
Published in:The Journal of biological chemistry 2002-04, Vol.277 (17), p.14894-14901
Main Authors: Mills, Denise A, Schmidt, Bryan, Hiser, Carrie, Westley, Erica, Ferguson-Miller, Shelagh
Format: Article
Language:English
Subjects:
Electron Transport Complex IV - antagonists & inhibitors
Electron Transport Complex IV - chemistry
Electron Transport Complex IV - metabolism
Membrane Potentials
Models, Molecular
Protein Conformation
Rhodobacter sphaeroides
Rhodobacter sphaeroides - enzymology
Zinc - pharmacology
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Summary:Like many voltage-sensitive ion pumps, cytochrome c oxidase is inhibited by zinc. Binding of zinc to the outside surface of Rhodobacter sphaeroides cytochrome c oxidase inhibits the enzyme with a K(I) of < or = 5 microm when the enzyme is reconstituted into phospholipid vesicles in the presence of a membrane potential. In the absence of a membrane potential and a pH gradient, millimolar concentrations of zinc are required to inhibit. This differential inhibition causes a dramatic increase in the respiratory control ratio from 6 to 40 for wild-type oxidase. The external zinc inhibition is removed by EDTA and is not competitive with cytochrome c binding but is competitive with protons. Only Cd(2+) of the many metals tested (Mg(2+), Mn(2+), Ca(2+), Ba(2+), Li(2+), Cs(2+), Hg(2+), Ni(2+), Co(2+), Cu(2+) Tb(3+), Tm(3+)) showed inhibitory effects similar to Zn(2+). Proton pumping is slower and less efficient with zinc. The results suggest that zinc inhibits proton movement through a proton exit path, which can allow proton back-leak at high membrane potentials. The physiological and mechanistic significance of proton movement in the exit pathway and its blockage by zinc is discussed in terms of regulation of the efficiency of energy transduction.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111922200