1P84

HDBT inhibited Yeast Cytochrome bc1 Complex

Summary for 1P84

• Entry DOI: 10.2210/pdb1p84/pdb
• Related: 1ezv 1kb9 1kyo
• Descriptor: Ubiquinol-cytochrome C reductase complex core protein I, Heavy Chain (Vh) Of Fv-Fragment, Light Chain (Vl) Of Fv-Fragment, ... (21 entities in total)
• Functional Keywords: cytochrome bc1 complex, complex iii, ubiquinol, cytochrome c oxidoreductase, hydroxyquinone, hhdbt, qo site, phospholipid, membrane protein, oxidoreductase
• Biological source: Mus musculus (house mouse); More
• Cellular location: Mitochondrion inner membrane : P07256 P07257 P00127 P00128 P08525 P22289; Mitochondrion inner membrane ; Multi-pass membrane protein : P00163; Mitochondrion inner membrane; Single-pass membrane protein; Intermembrane side: P07143; Mitochondrion inner membrane ; Single-pass membrane protein : P08067
• Total number of polymer chains: 11
• Total formula weight: 252736.10

Authors

Palsdottir, H.,Lojero, C.G.,Trumpower, B.L.,Hunte, C. (deposition date: 2003-05-06, release date: 2003-07-29, Last modification date: 2024-10-30)

Primary citation

Palsdottir, H.,Lojero, C.G.,Trumpower, B.L.,Hunte, C.
Structure of the yeast cytochrome bc1 complex with a hydroxyquinone anion Qo site inhibitor bound
J.Biol.Chem., 278:31303-31311, 2003

PubMed Abstract: Bifurcated electron transfer during ubiquinol oxidation is the key reaction of cytochrome bc1 complex catalysis. Binding of the competitive inhibitor 5-n-heptyl-6-hydroxy-4,7-dioxobenzothiazole to the Qo site of the cytochrome bc1 complex from Saccharomyces cerevisiae was analyzed by x-ray crystallography. This alkylhydroxydioxobenzothiazole is bound in its ionized form as evident from the crystal structure and confirmed by spectroscopic analysis, consistent with a measured pKa = 6.1 of the hydroxy group in detergent micelles. Stabilizing forces for the hydroxyquinone anion inhibitor include a polarized hydrogen bond to the iron-sulfur cluster ligand His181 and on-edge interactions via weak hydrogen bonds with cytochrome b residue Tyr279. The hydroxy group of the latter contributes to stabilization of the Rieske protein in the b-position by donating a hydrogen bond. The reported pH dependence of inhibition with lower efficacy at alkaline pH is attributed to the protonation state of His181 with a pKa of 7.5. Glu272, a proposed primary ligand and proton acceptor of ubiquinol, is not bound to the carbonyl group of the hydroxydioxobenzothiazole ring but is rotated out of the binding pocket toward the heme bL propionate A, to which it is hydrogen-bonded via a single water molecule. The observed hydrogen bonding pattern provides experimental evidence for the previously proposed proton exit pathway involving the heme propionate and a chain of water molecules. Binding of the alkyl-6-hydroxy-4,7-dioxobenzothiazole is discussed as resembling an intermediate step of ubiquinol oxidation, supporting a single occupancy model at the Qo site.

PubMed: 12782631
DOI: 10.1074/jbc.M302195200

Experimental method

X-RAY DIFFRACTION (2.5 Å)