Short-chain dehydrogenases/reductases (SDR).

作者: Hans Jörnvall , Bengt Persson , Maria Krook , Silvia Atrian , Roser Gonzalez-Duarte

DOI: 10.1021/BI00018A001

关键词: CofactorProtein familyStereochemistryChemistryActive siteShort-chain dehydrogenaseProtein structureSequence alignmentHydroxysteroid DehydrogenasesDehydrogenase

摘要: 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 the 15-30% level, indicating early duplicatory origins extensive divergence. In addition, another of 22 with extended chains exhibits part-chain SDR relationships represents no less than three EC classes. Furthermore, subforms species variants are known both families. combined superfamily, one is strictly conserved ascribed crucial enzymatic function (Tyr 151 in numbering system human NAD(+)-linked prostaglandin dehydrogenase). Such for Tyr general supported also by chemical modifications, site-directed mutagenesis, an active site position those tertiary structures that have been characterized. A lysine four residues downstream largely conserved. model catalysis available on basis these two residues. Binding coenzyme, NAD(H) or NADP(H), N-terminal part molecules, where common GlyXXXGlyXGly pattern occurs. Two established X-ray crystallography show one-domain subunit seven eight beta-strands. Conformational patterns similar, except variations C-terminal parts. Additional occur chains. Some molecules under more name, has shown be susceptible native, modification, producing reduced Schiff base adducts pyruvate other metabolic keto derivatives. Most dimers tetramers. analyzed, area major contacts involves long alpha-helices (alpha E, alpha F) similar apparently strong interactions. Future possibilities include verification proposed reaction mechanism tracing additional relationships, perhaps dehydrogenases illustrate value comparisons diversified research generating unexpected discoveries.

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