3H1L: Chicken cytochrome BC1 complex with ascochlorin bound at QO and QI sites

Citation:
Abstract
Ascochlorin is an isoprenoid antibiotic that is produced by the phytopathogenic fungus Ascochyta viciae. Similar to ascofuranone, which specifically inhibits trypanosome alternative oxidase by acting at the ubiquinol binding domain, ascochlorin is also structurally related to ubiquinol. When added to the mitochondrial preparations isolated from rat liver, or the yeast Pichia (Hansenula) anomala, ascochlorin inhibited the electron transport via CoQ in a fashion comparable to antimycin A and stigmatellin, indicating that this antibiotic acted on the cytochrome bc(1) complex. In contrast to ascochlorin, ascofuranone had much less inhibition on the same activities. On the one hand, like the Q(i) site inhibitors antimycin A and funiculosin, ascochlorin induced in H. anomala the expression of nuclear-encoded alternative oxidase gene much more strongly than the Q(o) site inhibitors tested. On the other hand, it suppressed the reduction of cytochrome b and the generation of superoxide anion in the presence of antimycin A(3) in a fashion similar to the Q(o) site inhibitor myxothiazol. These results suggested that ascochlorin might act at both the Q(i) and the Q(o) sites of the fungal cytochrome bc(1) complex. Indeed, the altered electron paramagnetic resonance (EPR) lineshape of the Rieske iron-sulfur protein, and the light-induced, time-resolved cytochrome b and c reduction kinetics of Rhodobacter capsulatus cytochrome bc(1) complex in the presence of ascochlorin demonstrated that this inhibitor can bind to both the Q(o) and Q(i) sites of the bacterial enzyme. Additional experiments using purified bovine cytochrome bc(1) complex showed that ascochlorin inhibits reduction of cytochrome b by ubiquinone through both Q(i) and Q(o) sites. Moreover, crystal structure of chicken cytochrome bc(1) complex treated with excess ascochlorin revealed clear electron densities that could be attributed to ascochlorin bound at both the Q(i) and Q(o) sites. Overall findings clearly show that ascochlorin is an unusual cytochrome bc(1) inhibitor that acts at both of the active sites of this enzyme.
PDB ID: 3H1LDownload
MMDB ID: 79129
PDB Deposition Date: 2009/4/12
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 3.21  Å
Source Organism:
Similar Structures:
Biological Unit for 3H1L: eicosameric; determined by author and by software (PISA)
Molecular Components in 3H1L
Label Count Molecule
Proteins (20 molecules)
2
Mitochondrial Ubiquinol-cytochrome-c Reductase Complex Core Protein I
Molecule annotation
2
Mitochondrial Ubiquinol-cytochrome-c Reductase Complex Core Protein 2
Molecule annotation
2
Cytochrome B(Gene symbol: CYTB)
Molecule annotation
2
Mitochondrial Cytochrome C1, Heme Protein
Molecule annotation
2
Cytochrome B-c1 Complex Subunit Rieske, Mitochondrial(Gene symbol: UQCRFS1)
Molecule annotation
2
Mitochondrial Ubiquinol-cytochrome C Reductase 14 KDA Protein
Molecule annotation
2
Mitochondrial Ubiquinol-cytochrome C Reductase Ubiquinone-binding Protein Qp-c
Molecule annotation
2
Mitochondrial Ubiquinol-cytochrome C Reductase 11 KDA Protein, Complex III Subunit Viii
Molecule annotation
2
Cytochrome B-c1 Complex Subunit Rieske, Mitochondrial(Gene symbol: UQCRFS1)
Molecule annotation
2
Mitochondrial Ubiquinol-cytochrome C Reductase 7.2 KDA Protein
Molecule annotation
Chemicals (38 molecules)
1
6
2
12
3
4
4
4
5
4
6
2
7
2
8
2
9
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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