Structures of the BC 1 Complex Reveal Dynamic Aspects of Mechanism

Structures for the bc1 complex (1) show several features of interest to catalysis at the Qo-site. The iron sulfur protein (ISP) occurs in several different positions: at a catalytic interface on cytochrome (cyt) b close to the Qo-site, in H-bond contact with a heme propionate of cyt c1, or in several intermediate positions (1–3). The Qo-site is a bifurcated volume, in which myxothiazol and MOA-inhibitors bind in a proximal domain near heme bL, but stigmatellin and UHDBT bind in a distal domain, where they interact with the ISP docked on cyt b. The structures also allow for the first time insights into the functional significance of mutations that modify turn-over or inhibitor binding. These structural observations have led us to suggest several new mechanistic features for the operation of the Qo-site, and have suggested experiments to test these, some of which we report here.