SHORT-CHAIN DEHYDROGENASES REDUCTASES (SDR)
SHORT-CHAIN DEHYDROGENASES REDUCTASES (SDR)
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DOI：
10.1021/bi00018a001
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发表时间：
1995-05-09
期刊：
影响因子：
2.9
通讯作者：
GHOSH, D
中科院分区：
文献类型：
--
作者：
JORNVALL, H;PERSSON, B;GHOSH, D
短链淀粉酶/还原酶（SDR）构成了一个大的蛋白质家族。目前，至少有57个特征性的高度不同的酶属于这个家族，并且通常仅在15-30%的水平上表现出残基同一性，这表明早期的重复起源和广泛的分歧。此外，另一个家族的22个酶与延长的蛋白质链表现出部分链SDR的关系，并代表酶不少于三个EC类。此外，已知两个科的亚型和种变体。在结合的SDR超家族中，只有一个残基是严格保守的，并被认为是关键的酶功能（人NAD（+）-连接的前列腺素脱氢酶的编号系统中的Tyr 151）。SDR酶中该Tyr残基的这种功能通常也得到化学修饰、定点诱变和已表征的那些三级结构中的活性位点位置的支持。下游四个残基的赖氨酸残基也很大程度上是保守的。一个模型的催化作用的基础上，这两个残基。辅酶NAD（H）或NADP（H）的结合在分子的N-末端部分，在那里出现共同的GlyXXXGlyXGly模式。通过X射线晶体学建立的两种SDR酶显示具有七至八条β链的单结构域亚基。构象模式是高度相似的，除了在C-末端部分的变化。在具有延伸链的家族中出现额外的结构。一些SDR分子已知有一个以上的名称，并且其中一种酶已被证明对天然的化学修饰敏感，与丙酮酸和其他代谢酮衍生物产生还原的席夫碱加合物。大多数SDR酶是二聚体和四聚体。在这些分析中，主要亚基接触的区域涉及两个长的α-螺旋（α E，α F）在类似的和明显强的亚基相互作用。未来的可能性包括验证所提出的反应机制和追踪其他关系，也许还与其他蛋白质家族。短链酶说明了比较和多样化研究在产生意想不到的发现方面的价值。
Short-chain dehydrogenases/reductases (SDR) constitute a large protein family. Presently, at least 57 characterized, highly different enzymes belong to this family and typically exhibit residue identities only at the 15-30% level, indicating early duplicatory origins and extensive divergence. In addition, another family of 22 enzymes with extended protein chains exhibits part-chain SDR relationships and represents enzymes of no less than three EC classes. Furthermore, subform and species variants are known of both families. In the combined SDR superfamily, only one residue is strictly conserved and ascribed a,crucial enzymatic function (Tyr 151 in the numbering system of human NAD(+)-linked prostaglandin dehydrogenase). Such a function for this Tyr residue in SDR enzymes in general is supported also by chemical modifications, site-directed mutagenesis, and an active site position in those tertiary structures that have been characterized. A lysine residue four residues downstream is also largely conserved. A model for catalysis is available on the basis of these two residues. Binding of the coenzyme, NAD(H) or NADP(H), is in the N-terminal part of the molecules, where a common GlyXXXGlyXGly pattern occurs. Two SDR enzymes established by X-ray crystallography show a one-domain subunit with seven to eight beta-strands. Conformational patterns are highly similar, except for variations in the C-terminal parts. Additional structures occur in the family with extended chains. Some of the SDR molecules are known under more than one name, and one of the enzymes has been shown to be susceptible to native, chemical modification, producing reduced Schiff base adducts with pyruvate and other metabolic keto derivatives, Most SDR enzymes are dimers and tetramers. In those analyzed, the area of major subunit contacts involves two long alpha-helices (alpha E, alpha F) in similar and apparently strong subunit interactions. Future possibilities include verification of the proposed reaction mechanism and tracing of additional relationships, perhaps also with other protein families. Short-chain dehydrogenases illustrate the value of comparisons and diversified research in generating unexpected discoveries.