Article
A rational approach to Re-engineer cytochrome P450 2B1 regioselectivity based on the crystal structure of cytochrome P450 2C5.
The Journal of biological chemistry - 9 May 2003
Kumar Santosh, Scott Emily E, Liu Hong, Halpert James R
Abstract excerpt
The regioselectivity for progesterone hydroxylation by cytochrome P450 2B1 was re-engineered based on the x-ray crystal structure of cytochrome P450 2C5. 2B1 is a high K(m) progesterone 16alpha-hydroxylase, whereas 2C5 is a low K(m) progesterone 21-hydroxylase. Initially, nine individual 2B1 active-site residues were changed to the corresponding 2C5 residues, and the mutants were purified from an Escherichia coli...
Topics
- Animals
- Binding Sites
- Crystallography, X-Ray
- Cytochrome P-450 CYP2B1
- Hydroxylation
- Models, Molecular
- Mutagenesis, Site-Directed
- Mutation
- Protein Conformation
- Rabbits
- Rats
- Recombinant Proteins
- Steroid Hydroxylases
- Structure-Activity Relationship
- Substrate Specificity