Download MendeleyStructural insights from a P450 Carrier Protein complex reveal how specificity is achieved in the P450(BioI) ACP complex.
Cryle, M.J., Schlichting, I.(2008) Proc Natl Acad Sci U S A 105: 15696-15701
- PubMed: 18838690
- DOI: https://doi.org/10.1073/pnas.0805983105
- Primary Citation of Related Structures:
3EJB, 3EJD, 3EJE - PubMed Abstract:
Cytochrome P450(BioI) (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 P450(BioI) in complex with three different length fatty acyl-ACP (Escherichia coli) ligands show that P450(BioI) 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 P450(BioI)-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.
Organizational Affiliation:
Department of Biomolecular Mechanisms, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany. [email protected]
