Short-chain dehydrogenases/reductases (SDR): the 2002 update.

Abstract:

: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.

journal_name

Chem Biol Interact

authors

Oppermann U,Filling C,Hult M,Shafqat N,Wu X,Lindh M,Shafqat J,Nordling E,Kallberg Y,Persson B,Jörnvall H

doi

10.1016/s0009-2797(02)00164-3

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

247-53

eissn

0009-2797

issn

1872-7786

pii

S0009279702001643

journal_volume

143-144

pub_type

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