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Amino acid residues that determine functional specificity of NADP‐ and NAD‐dependent isocitrate and isopropylmalate dehydrogenases
Author(s) -
Kalinina Olga V.,
Gelfand Mikhail S.
Publication year - 2006
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21027
Subject(s) - cofactor , nad+ kinase , biochemistry , substrate (aquarium) , isocitrate dehydrogenase , substrate specificity , enzyme , amino acid , stereochemistry , chemistry , biology , ecology
Isocitrate and isopropylmalalte dehydrogenases are homologous enzymes important for the cell metabolism. They oxidize their substrates using NAD or NADP as cofactors. Thus, they have two specificities, towards the substrate and the cofactor, appearing in three combinations. Although many three‐dimensional (3D) structures are resolved, identification of amino acids determining these specificities remains a challenge. We present computational identification and analysis of specificity‐determining positions (SDPs). Besides many experimentally proven SDPs, we predict new SDPs, for example, four substrate‐specific positions (103Leu, 105Thr, 337Ala, and 341Thr in IDH from E. coli ) that contact the cofactor and may play a role in the recognition process. Proteins 2006. © 2006 Wiley‐Liss, Inc.