The mode of action of stigmatellin, a new inhibitor of the cytochrome b-c1 segment of the respiratory chain

The chromone inhibitor stigmatellin ‐ binding to the ubiquinol oxidation center at the C‐side of the mitochondrial membrane

“…However, a difference m the precise mode of actron of strgmatellm and myxothrazol was revealed by the followmg two lines of observation: (i) several mutant strams of Saccharomyces cerevtszae resrstant to myxothrazol [4] exhibited no cross resistance to strgmatelhn 131; (11) cyt. b reduction behavior m the presence of st~gmatell~n plus antlmycln was drfferent [3] from that m the presence of myxothlazol plus antimycm [5).…”

“…These observations mdrcate that a functional Q0 binding sue requires both the cyt. b and Rteske iron-sulfur domain to be m certain specific conformattons or alteratton m one domam IS transferred to the other of the Q0 bmdmg site These two poss~b~l~t~es are being exammed usmg various stigmatelhn derivatives which grve rise to varying levels of mhibmon on the NADH oxtdatron by beef heart submttochondrial partrcles [3].…”

“…Its chemical structure has been determined [1,2] The molecule IS composed of a chromone rmg, substrtuted by a hydroxy, a methyl and two methoxy, and linked to an alkenyl side cham substituted by two methoxy and 3 methyl groups. The bmdmg and mhrbrtory effects of stlgmatellln have been shown to be drfferent from antrmycm, but closely resemble those of myxothrazol [3]. Both strgmatelhn and myxothrazol [4,5] bmd very trghtly to the complex (apparent & < 10-" M) wrth a storchrometry of one per cytochrome (cyt.)…”

Electronic Connection Between the Quinone and CytochromecRedox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

“…Some of these compounds (such as myxothiazol, stigmatellin, or antimycin) (262,247,248) are naturally produced by certain bacteria. Many Q o site inhibitors (such as strobilurin derivatives or famoxadone) are widely used in agriculture as pesticides because they are efficient fungicides but are, at the same time, relatively less toxic for mammals.…”

The Small Subunit AroB of Arsenite Oxidase

“…Three-dimensional structures and EPR studies with stigmatellin, dibromothymoquinone, and UHDBT have confirmed this interaction (22, 35, 46 -51). All these inhibitors are quinol analogs considered to be structural mimics of quinols or semiquinones (52,53). The structurally close relationship between the AroB-subunit and its counterpart from Rieske-cyt b complexes as well as the conservation of a pK-value close to 8 for Aro-Rieskes studied in this work led us to test the effects of Rieske-cyt b complex inhibitors on the Aro.…”