Analysis of the binding of p-chlorophenyl-methoxybenzyl-ketoxime (CPMB-oxime) to mitochondrial cytochrome c reductase.
Cytochrome c reductase is inhibited by p-chlorophenyl-methoxybenzyl-ketoxime (CPMB-oxime). CPMB-oxime induces a red-shift of the reduced spectrum of cytochrome b. The inhibitor blocks the oxidation of ubihydroquinone at the QP center of this enzyme in a non-competitive way. The binding stoichiometry equals one inhibitor molecule per Qp center. The apparent Kd in a red-shift assay was 6.9 +/- 0.6 microM. All binding characteristics analysed in this study were very similar to those of the E-beta-methoxyacrylate inhibitors, although the chemical structure is different from these inhibitors. This result is interpreted as a support for the inhibitory mechanism based on the model of a 'catalytic switch' proposed recently for the E-beta-methoxyacrylate inhibitors (MOA-inhibitors (Brandt and von Jagow, Eur. J. Biochem.
Brandt
U
U
Universität Frankfurt, Zentrum der Biologischen Chemie, Germany.
von Jagow
G
G
D000179:Acrylates / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002417:Cattle; D003573:Cytochrome b Group / Q000378:metabolism; D003575:Cytochromes c1 / Q000378:metabolism; D004579:Electron Transport; D008929:Mitochondria, Heart / Q000201:enzymology*; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010084:Oxidation-Reduction; D010091:Oximes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet
D000179:Acrylates; D003573:Cytochrome b Group; D010091:Oximes; C070573:4-chlorophenylmethoxybenzyl ketoxime; D003575:Cytochromes c1; D009245:NADH Dehydrogenase