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 Interactjournal_title
Chemico-biological interactionsauthors
Oppermann U,Filling C,Hult M,Shafqat N,Wu X,Lindh M,Shafqat J,Nordling E,Kallberg Y,Persson B,Jörnvall Hdoi
10.1016/s0009-2797(02)00164-3subject
Has Abstractpub_date
2003-02-01 00:00:00pages
247-53eissn
0009-2797issn
1872-7786pii
S0009279702001643journal_volume
143-144pub_type
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