Studies on the effect of stigmatellin derivatives on cytochrome b and the Rieske iron-sulfur cluster of cytochrome c reductase from bovine heart mitochondria.

Stigmatellin and its derivatives represent a third class of Qo site inhibitors besides the hydroxyquinone derivatives and the E-beta-methoxyacrylate (MOA) inhibitors [von Jagow and Link (1986) Methods Enzymol. 126, 253-271]. The stigmatellins consist of a chromone ring system connected to an substituted alkenyl side chain. Alterations in the side chain, i.e. saturation of the C = C double bonds, shift of a methoxy group or loss of the methyl groups, specifically affect the binding characteristics. Besides changing the red shift spectrum of reduced cytochrome b566 and the EPR spectrum of the Rieske iron-sulfur cluster, the side chain alterations diminish the binding affinity and the extent of the midpoint potential shift of the iron-sulfur protein. Thus, the side chain of the molecule makes an essential contribution to the binding energy and is not necessary solely for partitioning the molecule into the hydrophobic phase, as assumed so far.