Kalinina Olga V, Gelfand Mikhail S
Department of Bioengineering and Bioinformatics, Moscow State University, Moscow, Russia.
Proteins. 2006 Sep 1;64(4):1001-9. doi: 10.1002/prot.21027.
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.
异柠檬酸脱氢酶和异丙基苹果酸脱氢酶是对细胞代谢很重要的同源酶。它们利用NAD或NADP作为辅因子来氧化其底物。因此，它们对底物和辅因子有两种特异性，呈现出三种组合。尽管许多三维（3D）结构已得到解析，但确定决定这些特异性的氨基酸仍然是一项挑战。我们展示了对特异性决定位置（SDPs）的计算识别和分析。除了许多经实验验证的SDPs外，我们还预测了新的SDPs，例如，四个底物特异性位置（大肠杆菌IDH中的103Leu、105Thr、337Ala和341Thr），它们与辅因子接触并可能在识别过程中发挥作用。
