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Publication Abstract from PubMed

The Complex III or cytochrome bc1 (cyt bc1) complex constitutes an integral part of the respiratory chain of most aerobic organisms and of the photosynthetic apparatus of anoxygenic purple bacteria. The function of cyt bc1 is to couple the reaction of electron transfer (ET) from ubiquinol to cytochrome c to proton pumping across the membrane. Mechanistically, the ET reaction requires docking of its Rieske iron-sulfur protein (ISP) subunit to the quinol oxidation (QP) site of the complex. Formation of an H-bond between the ISP and the bound substrate was proposed to mediate the docking. Here we show that the binding of oxazolidinedione-type inhibitors famoxadone, jg144, and fenamidone induces docking of the ISP to the QP site in the absence of the H-bond formation both in mitochondrial and bacterial cyt bc1 complexes, demonstrating that ISP docking is independent of the proposed H-bond. The binding of oxazolidinedione-type inhibitors to cyt bc1 of different species reveals a toxophore that appears to interact optimally with residues in the QP site. The effect of modifications or additions to the toxophore on the binding of cyt bc1 from different species could not be predicted from structure-based sequence alignment, as demonstrated by the altered binding mode of famoxadone to the bacterial cyt bc1.

Hydrogen Bonding to the substrate is not required for Rieske iron-sulfur protein docking to the quinol oxidation site of complex III.,Esser L, Zhou F, Zhou Y, Xiao Y, Tang WK, Yu CA, Qin Z, Xia D J Biol Chem. 2016 Oct 7. pii: jbc.M116.744391. PMID:27758861^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.