Genetic Selection as a Tool in Mechanistic Enzymology and Protein Design
Protein design is a challenging problem. We do not fully understand the rules of protein folding, and our knowledge of structure-function relationships in these macromolecules is at best incomplete. It is consequently not yet possible to specify the sequence of a polypeptide with any reasonable expectation that it will adopt a unique tertiary fold, much less recognize another molecule with high selectivity or catalyze a chemical reaction.
KeywordsProtein Design Ether Oxygen Hydrogen Bonding Distance Catalytic Antibody Claisen Rearrangement
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- Bell IM, Hilvert D (1994) New biocatalysts via chemical modification. In: Behr J-P (ed) The lock-and-key principle. Wiley, Sussex, pp 73–88Google Scholar
- Bowdish K, Tang Y, Hicks JB, Hilvert D (1991) Yeast expression of a catalytic antibody with chorismate mutase activity. J Biol Chem 266:11910–11908Google Scholar
- Chook YM, Gray JV, Ke H, Lipscomb WN (1994) The monofunctional chorismate mutase from Bacillus subtilis. Structure determination of chorismate mutase and its complexes with a transition state analog and prephenate, and implications for the mechanism of the enzymatic reaction. J Mol Biol 240:476–500PubMedCrossRefGoogle Scholar
- Hilvert D (2000) Critical analysis of antibody catalysis. Annu Rev Biochem 69 (in press)Google Scholar
- Sauer RT (1996) Protein folding from a combinatorial perspective. Fold Des LR27-R30Google Scholar
- Tang Y (1996) Evolutionary studies with a catalytic antibody. PhD, Scripps Research InstituteGoogle Scholar
- Weiss U, Edwards JM (1980) The biosynthesis of aromatic amino compounds. Wiley, New YorkGoogle Scholar