title: Amino acid residues that determine functional specificity of NADP- and NAD-dependent isocitrate and isopropylmalate dehydrogenases.
abstract: 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.
authors.affiliation: Department of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Kalinina
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Gelfand
mesh_terms: D050539:3-Isopropylmalate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D019281:Dimerization; D007521:Isocitrate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010802:Phylogeny; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D009243:NAD; D009249:NADP; D007521:Isocitrate Dehydrogenase; D050539:3-Isopropylmalate Dehydrogenase