Variation on a theme of SDR. dTDP-6-deoxy-L- lyxo-4-hexulose reductase (RmlD) shows a new Mg2+-dependent dimerization mode

• Published in: Structure (London) Vol. 10; no. 6; p. 773
• Main Authors: Blankenfeldt, Wulf, Kerr, Iain D, Giraud, Marie-France, McMiken, Helen J, Leonard, Gordon, Whitfield, Chris, Messner, Paul, Graninger, Michael, Naismith, James H
• Format: Journal Article
• Language: English
• Published: United States 01.06.2002
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Binding Sites; Dimerization; Magnesium - metabolism; Mutagenesis, Site-Directed; NAD - metabolism; NADP - metabolism; Protein Structure, Tertiary; Salmonella enterica - enzymology; Salmonella enterica - metabolism; Sugar Alcohol Dehydrogenases - chemistry; Sugar Alcohol Dehydrogenases - metabolism
• ISSN: 0969-2126
• DOI: 10.1016/S0969-2126(02)00770-0

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.