Abstract
Cytochrome P450BioI (CYP107H1) from the biotin operon of Bacillus subtilis forms a seven-carbon diacid through a multistep oxidative cleavage of a fatty acid linked to acyl carrier protein (ACP). Crystal structures of P450BioI in complex with three different length fatty acyl-ACP (Escherichia coli) ligands show that P450BioI binds the fatty acid such as to force the carbon chain into a U-shape above the active site heme. This positions the C7 and C8 carbons for oxidation, with a large additional cavity extending beyond the heme to accommodate the methyl termini of fatty acids beyond the site of cleavage. The structures explain the experimentally observed lack of stereo- and regiospecificity in the hydroxylation and cleavage of free fatty acids. The P450BioI-ACP complexes represent the only structurally characterized P450-carrier protein complexes to date, which has allowed the generation of a model of the interaction of the vancomycin biosynthetic P450 OxyB with its proposed carrier protein bound substrate.
Original language | English |
---|---|
Pages (from-to) | 15696-15701 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 105 |
Issue number | 41 |
DOIs | |
Publication status | Published - 14 Oct 2008 |
Externally published | Yes |
Keywords
- Acyl carrier protein
- Biotin biosynthesis
- Crystal structure
- Cytochrome P450
- Protein-protein interaction