1NTK: Crystal Structure Of Mitochondrial Cytochrome Bc1 In Complex With Antimycin A1

Citation:
Abstract
Cytochrome bc(1) is an integral membrane protein complex essential to cellular respiration and photosynthesis. The Q cycle reaction mechanism of bc(1) postulates a separated quinone reduction (Q(i)) and quinol oxidation (Q(o)) site. In a complete catalytic cycle, a quinone molecule at the Q(i) site receives two electrons from the b(H) heme and two protons from the negative side of the membrane; this process is specifically inhibited by antimycin A and NQNO. The structures of bovine mitochondrial bc(1) in the presence or absence of bound substrate ubiquinone and with either the bound antimycin A(1) or NQNO were determined and refined. A ubiquinone with its first two isoprenoid repeats and an antimycin A(1) were identified in the Q(i) pocket of the substrate and inhibitor bound structures, respectively; the NQNO, on the other hand, was identified in both Q(i) and Q(o) pockets in the inhibitor complex. The two inhibitors occupied different portions of the Q(i) pocket and competed with substrate for binding. In the Q(o) pocket, the NQNO behaves similarly to stigmatellin, inducing an iron-sulfur protein conformational arrest. Extensive binding interactions and conformational adjustments of residues lining the Q(i) pocket provide a structural basis for the high affinity binding of antimycin A and for phenotypes of inhibitor resistance. A two-water-mediated ubiquinone protonation mechanism is proposed involving three Q(i) site residues His(201), Lys(227), and Asp(228).
PDB ID: 1NTKDownload
MMDB ID: 24664
PDB Deposition Date: 2003/1/30
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
Similar Structures:
Biological Unit for 1NTK: 22-meric; determined by author and by software (PISA,PQS)
Molecular Components in 1NTK
Label Count Molecule
Proteins (22 molecules)
2
Ubiquinol-cytochrome C Reductase Complex Core Protein I, Mitochondrial(Gene symbol: UQCRC1)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Complex Core Protein 2, Mitochondrial(Gene symbol: UQCRC2)
Molecule annotation
2
Cytochrome B(Gene symbol: CYTB)
Molecule annotation
2
Cytochrome C1(Gene symbol: CYC1)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Iron-sulfur Subunit, Mitochondrial(Gene symbol: UQCRFS1)
Molecule annotation
2
Ubiquinol-cytochrome C Reductase Complex 14 KDA Protein(Gene symbol: UQCRB)
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 8 KDA Protein(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 (10 molecules)
1
6
2
2
3
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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