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Predicting amino acid residues responsible for enzyme specificity solely from protein sequences
Author(s) -
Shaw Eudean,
Dordick Jonathan S.
Publication year - 2002
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.10289
Subject(s) - amino acid , amino acid residue , computational biology , biochemistry , enzyme , biocatalysis , substrate specificity , modular design , chemistry , superfamily , substrate (aquarium) , peptide sequence , biology , computer science , gene , catalysis , reaction mechanism , ecology , operating system
We describe a general, modular method for developing protocols to identify the amino acid residues that most likely define the division of a protein superfamily into two subsets. As one possibility, we use P ROBE to gather superfamily members and perform an ungapped alignment. We then use a modified B LOSUM62 substitution matrix to determine the discriminating power of each column of aligned residues. The overall method is particularly useful for predicting amino acids responsible for substrate or binding specificity when no structures are available. We apply our method to three pairs of protein classes in three different superfamilies, and present our results, some of which have been experimentally verified. This approach may accelerate the elucidation of enzymic substrate specificity, which is critical for both mechanistic insights into biocatalysis and ultimate application. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 295–300, 2002.