title: Mutational remodeling of enzyme specificity.
abstract: With the advent of genetic engineering techniques has come the ability to modify proteins as desired. Given this stunning capability, the question remains what residues should be altered, and how should they be changed to achieve a particular specificity pattern. The goals of such modifications are likely to fall into either of two categories: probing the function of a protein or attempting to alter its properties. In either case, our understanding of the consequences of a mutation, as ascertained by our ability to predict the results, is currently quite limited. The problem is extraordinarily complex; our understanding of how to calculate the energetics involved is still incomplete, and we are just beginning to accumulate experimental data which may help guide us. On the positive side, theoretical methods are now being developed and refined that should prove useful in the drive to engineer enzyme specificity. What may be most important at this juncture is to expand the experimental database interrelating sequence, function, and structure. That is, there should be a concerted effort to combine functional analysis of mutant proteins with structural analysis. Only from this combined examination of the effects of mutations can sufficient data be accumulated to test and improve both qualitative and quantitative approaches or methods for remodeling enzyme specificity.
authors.forename: R
authors.initials: R
authors.lastname: Bone
authors.forename: D A
authors.initials: DA
authors.lastname: Agard
mesh_terms: D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics*; D006860:Hydrogen Bonding; D007532:Isoleucine / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D016296:Mutagenesis; D011487:Protein Conformation; D015202:Protein Engineering; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D004798:Enzymes; D007532:Isoleucine; D001219:Aspartate Aminotransferases; D012697:Serine Endopeptidases; C021826:myxobacter alpha-lytic proteinase; C022325:aspartic proteinase A; D016282:Aspartic Acid Endopeptidases; D007930:Leucine