期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 143, 期 -, 页码 247-253出版社
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0009-2797(02)00164-3
关键词
short-chain dehydrogenases/reductases; structure-function relationships; hydroxysteroid dehydrogenase; reaction mechanism; metabolic disease
Short-chain dehydrogenases/reductases (SDR) form a large, functionally heterogeneous protein family presently with about 3000 primary and about 30 3D structures deposited in databases. Despite low sequence identities between different forms (about 15-30%), the 3D structures display highly similar alpha/beta folding patterns with a central beta-sheet, typical of the Rossmann-fold. Based on distinct sequence motifs functional assignments and classifications are possible, making it possible to build a general nomenclature system. Recent mutagenetic and structural studies considerably extend the knowledge on the general reaction mechanism, thereby establishing a catalytic tetrad of Asn-Ser-Tyr-Lys residues, which presumably form the framework for a proton relay system including the 2'-OH of the nicotinamide ribose, similar to the mechanism found in horse liver ADH. Based on their cellular functions, several SDR enzymes appear as possible and promising pharmacological targets with application areas spanning hormone-dependent cancer forms or metabolic diseases such as obesity and diabetes, and infectious diseases. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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