title: 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.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177, Stockholm, Sweden. udo.oppermann@mbb.ki.se
authors.forename: Udo
authors.initials: U
authors.lastname: Oppermann
authors.forename: Charlotta
authors.initials: C
authors.lastname: Filling
authors.forename: Malin
authors.initials: M
authors.lastname: Hult
authors.forename: Naeem
authors.initials: N
authors.lastname: Shafqat
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Wu
authors.forename: Monica
authors.initials: M
authors.lastname: Lindh
authors.forename: Jawed
authors.initials: J
authors.lastname: Shafqat
authors.forename: Erik
authors.initials: E
authors.lastname: Nordling
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kallberg
authors.forename: Bengt
authors.initials: B
authors.lastname: Persson
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010088:Oxidoreductases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D010088:Oxidoreductases