Evolution by Structure-Based Protein Recombination
Abstract
The computational algorithm SCHEMA was developed to estimate the disruption caused when amino acid residues that interact in the three-dimensional structure of a protein are inherited from different parents upon recombination. If the folded structure is retained, the new chimeric sequences can display functional properties characteristic of the parents; they can also acquire entirely new functions. We are using SCHEMA to design chimeras of cytochrome P450 heme enzymes. In a preliminary study of 17 chimeras, we observed significant functional diversity: chimeras displayed altered substrate specificity profiles, a wide range in thermostabilities, up to a 40-fold increase in peroxidase activity, and ability to hydroxylate a substrate towards which neither parent shows detectable activity. SCHEMA-guided recombination can generate diverse sequences for exploring the evolution of function within a given protein structural framework.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA417404
Entities
People
- Frances Arnold
Organizations
- California Institute of Technology