1SQP: Crystal Structure Analysis Of Bovine Bc1 With Myxothiazol

Citation:
Abstract
Cytochrome bc(1) is an integral membrane protein complex essential for cellular respiration and photosynthesis; it couples electron transfer from quinol to cytochrome c to proton translocation across the membrane. Specific bc(1) inhibitors have not only played crucial roles in elucidating the mechanism of bc(1) function but have also provided leads for the development of novel antibiotics. Crystal structures of bovine bc(1) in complex with the specific Q(o) site inhibitors azoxystrobin, MOAS, myxothiazol, stigmatellin and 5-undecyl-6-hydroxy-4,7-dioxobenzothiazole were determined. Interactions, conformational changes and possible mechanisms of resistance, specific to each inhibitor, were defined. Residues and secondary structure elements that are capable of discriminating different classes of Q(o) site inhibitors were identified for the cytochrome b subunit. Directions in the displacement of the cd1 helix of cytochrome b subunit in response to various Q(o) site inhibitors were correlated to the binary conformational switch of the extrinsic domain of the iron-sulfur protein subunit. The new structural information, together with structures previously determined, provide a basis that, combined with biophysical and mutational data, suggest a modification to the existing classification of bc(1) inhibitors. bc(1) inhibitors are grouped into three classes: class P inhibitors bind to the Q(o) site, class N inhibitors bind to the Q(i) site and the class PN inhibitors target both sites. Class P contains two subgroups, Pm and Pf, that are distinct by their ability to induce mobile or fixed conformation of iron-sulfur protein.
PDB ID: 1SQPDownload
MMDB ID: 35424
PDB Deposition Date: 2004/3/19
Updated in MMDB: 2014/11
Experimental Method:
x-ray diffraction
Resolution: 2.7  Å
Source Organism:
Similar Structures:
Biological Unit for 1SQP: 22-meric; determined by author and by software (PISA,PQS)
Molecular Components in 1SQP
Label Count Molecule
Proteins (22 molecules)
2
Ubiquinol-cytochrome-c Reductase Complex Core Protein I, Mitochondrial Precursor(Gene symbol: UQCRC1)
Molecule annotation
2
Ubiquinol-cytochrome-c Reductase Complex Core Protein 2, Mitochondrial Precursor(Gene symbol: UQCRC2)
Molecule annotation
2
Cytochrome B(Gene symbol: CYTB)
Molecule annotation
2
Cytochrome C1, Heme Protein, Mitochondrial(Gene symbol: CYC1)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Iron-sulfur Subunit, Mitochondrial Precursor (EC 1.10.2.2) (Rieske Iron-sulfur Protein) (Risp) [contains: Ubiquinol-cytochrome C Reductase 8 KDA Protein (Complex III Subunit Ix)](Gene symbol: UQCRFS1)
Molecule annotation
2
Sub6
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Complex Ubiquinone-binding Protein Qp-c(Gene symbol: UQCRQ)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Complex 11 KDA Protein(Gene symbol: UQCRH)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Iron-sulfur Subunit, Mitochondrial Precursor (EC 1.10.2.2) (Rieske Iron-sulfur Protein) (Risp) [contains: Ubiquinol-cytochrome C Reductase 8 KDA Protein (Complex III Subunit Ix)](Gene symbol: UQCRFS1)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Complex 7.2 KDA Protein(Gene symbol: UQCR10)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Complex 6.4 KDA Protein(Gene symbol: UQCR11)
Molecule annotation
Chemicals (24 molecules)
1
6
2
6
3
6
4
2
5
2
6
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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