Progress Toward the Rational Study of Enzyme Structure-Function Relationships

Abstract

This chapter discusses necessarily a snapshot of a very rapidly moving field to emphasize the generality of the approach by focusing on a few selected applications of various techniques of mutagenesis to studies of protein function. Although still in its infancy, the use of mutagenic techniques to create new proteins has allowed to gain many insights into the rules that relate amino acid sequence to three dimensional structure and function. Further applications and refinements of these approaches is anticipated to eventually lead to the ability for rational design of proteins for applications in medicine, industry, and commerce with a broad range of specifically tailored, novel, and useful properties. In general, target residues for mutagenic experiments are decided on the basis of existing structural or kinetic information: data from x-ray structures, chemical modification experiments, or from sequence comparisons may indicate sites that are of interest. Specific problems that have been addressed include determination of the roles of specific amino acids in catalysis and in substrate binding, in allosterism, in protein stability, in protein-protein interactions, and in protein-DNA interactions.