HOQNO interaction with cytochrome b in succinate:menaquinone oxidoreductase from Bacillus subtilis.
2-n-Heptyl 4-hydroxyquinoline-N-oxide (HOQNO) inhibits the succinate:quinone oxidoreductase activity of isolated and membrane-bound succinate:menaquinone oxidoreductase of B. subtilis. The inhibition pattern resembles closely that observed for alpha-thenoyltrifluoroacetone and carboxins in the mitochondrial succinate:ubiquinone oxidoreductase: ca. 90% of the activity is highly sensitive to HOQNO (Ki ca. 0.2 microM for the isolated enzyme) whereas the rest 10% proves to be resistant to the inhibitor. HOQNO binding is shown to perturb the absorption spectrum of the ferrous di-heme cytochrome b of the B. subtilis succinate:quinone oxidoreductase both in the alpha and Soret bands. In addition, the inhibitor is shown to bring about a negative shift of Em of the low-potential heme b. It is suggested that HOQNO interacts with a menasemiquinone binding site near the low-potential heme and suppresses the MQ.(-)-to-MQH2 step of the quinone reductase reaction but allows partly for the MQ-to-MQ.- transition to occur; dismutation of MQ. formed in the latter reaction to MQ and MQH2 may account for the 10% of the enzyme activity insensitive to HOQNO.
A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russian Federation.
I A
IA
Smirnova
C
C
Hägerhäll
A A
AA
Konstantinov
L
L
Hederstedt
D001412:Bacillus subtilis / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D003573:Cytochrome b Group / Q000378:metabolism*; D042963:Electron Transport Complex II; D006863:Hydrogen-Ion Concentration; D006912:Hydroxyquinolines / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013053:Spectrophotometry; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D003573:Cytochrome b Group; D006912:Hydroxyquinolines; D009097:Multienzyme Complexes; C001333:2-(n-heptyl)-4-hydroxyquinoline N-oxide; D010088:Oxidoreductases; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase