Crystallographic location of two Zn(2+)-binding sites in the avian cytochrome bc(1) complex.
The chicken mitochondrial ubiquinol cytochrome c oxidoreductase (bc(1) complex) is inhibited by Zn(2+) ions, but with higher K(i) ( approximately 3 microM) than the corresponding bovine enzyme. When equilibrated with mother liquor containing 200 microM ZnCl(2) for 7 days, the crystalline chicken bc(1) complex specifically binds Zn(2+) at 4 sites representing two sites on each monomer in the dimer. These two sites are close to the stigmatellin-binding site, taken to be center Q(o) of the Q-cycle mechanism, and are candidates for the inhibitory site. One binding site is actually in the hydrophobic channel between the Q(o) site and the bulk lipid phase, and may interfere with quinone binding. The other is in a hydrophilic area between cytochromes b and c(1), and might interfere with the egress of protons from the Q(o) site to the intermembrane aqueous medium. No zinc was bound near the putative proteolytic active site of subunits 1 and 2 (homologous to mitochondrial processing peptidase) under these conditions.
Berry
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lawrence Berkeley National Laboratory, University of California, USA. eaberry@lbl.gov
Zhang
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Bellamy
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Huang
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent; D002417:Cattle; D002645:Chickens; D002712:Chlorides / Q000494:pharmacology; D018360:Crystallography, X-Ray; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008666:Metalloendopeptidases / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology; D000096122:Mitochondrial Processing Peptidase
D002413:Cations, Divalent; D002712:Chlorides; D014450:Electron Transport Complex III; D008024:Ligands; D008666:Metalloendopeptidases; D015032:Zinc; D017967:Zinc Compounds; D000096122:Mitochondrial Processing Peptidase; C016837:zinc chloride