Structural insights from a P450 Carrier Protein complex reveal how specificity is achieved in the P450BioIACP complex
- 14 October 2008
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (41) , 15696-15701
- https://doi.org/10.1073/pnas.0805983105
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.Keywords
This publication has 40 references indexed in Scilit:
- Crystal structures and catalytic mechanism of cytochrome P450 StaP that produces the indolocarbazole skeletonProceedings of the National Academy of Sciences, 2007
- Oxidative Phenol Coupling Reactions Catalyzed by OxyB: A Cytochrome P450 from the Vancomycin Producing Organism. Implications for Vancomycin BiosynthesisJournal of the American Chemical Society, 2007
- Structural Studies of Fatty Acyl-(Acyl Carrier Protein) Thioesters Reveal a Hydrophobic Binding Cavity that Can Expand to Fit Longer SubstratesJournal of Molecular Biology, 2006
- The Structural Basis for Substrate Anchoring, Active Site Selectivity, and Product Formation by P450 PikC from Streptomyces venezuelaePublished by Elsevier ,2006
- Secondary-structure matching (SSM), a new tool for fast protein structure alignment in three dimensionsActa Crystallographica Section D-Biological Crystallography, 2004
- Coot: model-building tools for molecular graphicsActa Crystallographica Section D-Biological Crystallography, 2004
- Reactions Catalyzed by Bacterial Cytochromes P450Australian Journal of Chemistry, 2003
- Refinement of Macromolecular Structures by the Maximum-Likelihood MethodActa Crystallographica Section D-Biological Crystallography, 1997
- Biosynthesis of pimeloyl-CoA, a biotin precursor in Escherichia coli, follows a modified fatty acid synthesis pathway: 13C-labeling studiesJournal of the American Chemical Society, 1994
- Acyl Carrier ProteinPublished by Wiley ,1972