title: Variation on a theme of SDR. dTDP-6-deoxy-L- lyxo-4-hexulose reductase (RmlD) shows a new Mg2+-dependent dimerization mode.
abstract: dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmlD) catalyzes the final step in the conversion of dTDP-D-glucose to dTDP-L-rhamnose in an NAD(P)H- and Mg2+-dependent reaction. L-rhamnose biosynthesis is an antibacterial target. The structure of RmlD from Salmonella enterica serovar Typhimurium has been determined, and complexes with NADH, NADPH, and dTDP-L-rhamnose are reported. RmlD differs from other short chain dehydrogenases in that it has a novel dimer interface that contains Mg2+. Enzyme catalysis involves hydride transfer from the nicotinamide ring of the cofactor to the C4'-carbonyl group of the substrate. The substrate is activated through protonation by a conserved tyrosine. NAD(P)H is bound in a solvent-exposed cleft, allowing facile replacement. We suggest a novel role for the conserved serine/threonine residue of the catalytic triad of SDR enzymes.
authors.affiliation: The Centre for Biomolecular Sciences, The University, St. Andrews, KY16 9ST, Scotland, United Kingdom.
authors.forename: Wulf
authors.initials: W
authors.lastname: Blankenfeldt
authors.forename: Iain D
authors.initials: ID
authors.lastname: Kerr
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Giraud
authors.forename: Helen J
authors.initials: HJ
authors.lastname: McMiken
authors.forename: Gordon
authors.initials: G
authors.lastname: Leonard
authors.forename: Chris
authors.initials: C
authors.lastname: Whitfield
authors.forename: Paul
authors.initials: P
authors.lastname: Messner
authors.forename: Michael
authors.initials: M
authors.lastname: Graninger
authors.forename: James H
authors.initials: JH
authors.lastname: Naismith
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D019281:Dimerization; D008274:Magnesium / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019779:Salmonella enterica / Q000201:enzymology* / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D009243:NAD; D009249:NADP; D013401:Sugar Alcohol Dehydrogenases; C405941:thymidine diphosphate-6-deoxy-L-lyxo-4-hexulose reductase; D008274:Magnesium