title: Inhibitor binding changes domain mobility in the iron-sulfur protein of the mitochondrial bc1 complex from bovine heart.
abstract: We have analyzed crystal structures of cytochrome bc1 complexes with electron transfer inhibitors bound to the ubiquinone binding pockets Qi and/or Qo in the cytochrome b subunit. The presence or absence of the Qi inhibitor antimycin A did not affect the binding of the Qo inhibitors. Different subtypes of Qo inhibitors had dramatically different effects on the mobility of the extramembrane domain of the iron-sulfur protein (ISP): Binding of 5-undecyl-6-hydroxy-4, 7-dioxobenzothiazol and stigmatellin (subtype Qo-II and Qo-III, respectively) led to a fixation of the ISP domain on the surface of cytochrome b, whereas binding of myxothiazol and methoxyacrylate-stilbene (subtype Qo-I) favored release of this domain. The native structure has an empty Qo pocket and is intermediate between these extremes. On the basis of these observations we propose a model of quinone oxidation in the bc1 complex, which incorporates fixed and loose states of the ISP as features important for electron transfer and, possibly, also proton transport.
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75235-9050, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Xia
authors.forename: C A
authors.initials: CA
authors.lastname: Yu
authors.forename: J Z
authors.initials: JZ
authors.lastname: Xia
authors.forename: A M
authors.initials: AM
authors.lastname: Kachurin
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Deisenhofer
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism*; D011487:Protein Conformation; D014451:Ubiquinone / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D007506:Iron-Sulfur Proteins; D014451:Ubiquinone; D014450:Electron Transport Complex III