Department of Medical Biochemistry and Biophysics (MBB), Karolinska Institutet, SE-17177 Stockholm, Sweden.
Biochem Biophys Res Commun. 2010 May 21;396(1):125-30. doi: 10.1016/j.bbrc.2010.03.094.
Two large gene and protein superfamilies, SDR and MDR (short- and medium-chain dehydrogenases/reductases), were originally defined from analysis of alcohol and polyol dehydrogenases. The superfamilies contain minimally 82 and 25 genes, respectively, in humans, minimally 324 and 86 enzyme families when known lines in other organisms are also included, and over 47,000 and 15,000 variants in existing sequence data bank entries. SDR enzymes have one-domain subunits without metal and MDR two-domain subunits without or with zinc, and these three lines appear to have emerged in that order from the universal cellular ancestor. This is compatible with their molecular architectures, present multiplicity, and overall distribution in the kingdoms of life, with SDR also of viral occurrence. An MDR-zinc, when present, is often, but not always, catalytic. It appears also to have a structural role in inter-domain interactions, coenzyme binding and substrate pocket formation, as supported by domain variability ratios and ligand positions. Differences among structural and catalytic zinc ions may be relative and involve several states. Combined, the comparisons trace evolutionary properties of huge superfamilies, with partially redundant enzymes in cellular redox functions.
两个大型基因和蛋白质超家族，SDR 和 MDR（短链和中链脱氢酶/还原酶），最初是从醇和多元醇脱氢酶的分析中定义的。超家族在人类中分别至少包含 82 和 25 个基因，当包括其他生物体中的已知谱系时，分别至少包含 324 和 86 个酶家族，并且在现有序列数据库条目中包含超过 47,000 和 15,000 个变体。SDR 酶具有没有金属的单结构域亚基，而 MDR 酶具有没有或具有锌的双结构域亚基，这三条线似乎按照从通用细胞祖先出现的顺序出现。这与它们的分子结构、目前的多样性以及在生命王国中的整体分布相匹配，SDR 也存在于病毒中。当存在时，MDR-锌通常但不总是具有催化活性。它似乎在结构域相互作用、辅酶结合和底物口袋形成中也具有结构作用，这得到了结构域变异性比和配体位置的支持。结构和催化锌离子之间的差异可能是相对的，并涉及多个状态。综合起来，这些比较追踪了具有细胞氧化还原功能部分冗余酶的巨大超家族的进化特性。
