Open AccessTwo binding sites of inhibitors in NADH:ubiquinone oxidoreductase (complex I)
Author(s) -
FRIEDRICH Thorsten,
HEEK Petra,
LEIF Hans,
OHNISHI Tomoko,
FORCHE Edgar,
KUNZE Brigitte,
JANSEN Rolf,
TROWITZSCHKIENAST Wolfram,
HÖFLE Gerhard,
REICHENBACH Hans,
WEISS Hanns
Publication year - 1994
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1994.tb19985.x
Subject(s) - oxidoreductase , nadh dehydrogenase , biochemistry , neurospora crassa , electron transport complex i , biology , dehydrogenase , enzyme , stereochemistry , chemistry , protein subunit , mutant , gene
The effect of ten naturally occurring and two synthetic inhibitors of NADH:ubiquinone oxidoreductase (complex I) of bovine heart, Neurospora crassa and Escherichia coli and glucose:ubiquinone oxidoreductase (glucose dehydrogenase) of Gluconobacter oxidans was investigated. These inhibitors could be divided into two classes with regard to their specifity and mode of action. Class I inhibitors, including the naturally occuring piericidin A, annonin VI, phenalamid A 2 , aurachins A and B, thiangazole and the synthetic fenpyroximate, inhibit complex I from all three species in a partially competitive manner and glucose dehydrogenase in a competitive manner, both with regard to ubiquinone. Class II inhibitors including the naturally occuring rotenone, phenoxan, aureothin and the synthetic benzimidazole inhibit complex I from all species in an non‐competitive manner, but have no effect on the glucose dehydrogenase. Myxalamid PI could not be classified as above because it inhibits only the mitochondrial complex I and in a competitive manner. All inhibitors affect the electron‐transfer step from the high‐potential iron‐sulphur cluster to ubiquinone. Class I inhibitors appear to act directly at the ubiquinone‐catalytic site which is related in complex I and glucose dehydrogenase.