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

Structure. 2002 Jun;10(6):773-86. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Bacterial Proteins
  • NAD
  • NADP
  • Sugar Alcohol Dehydrogenases
  • thymidine diphosphate-6-deoxy-L-lyxo-4-hexulose reductase
  • Magnesium

Associated data

  • PDB/1KBZ
  • PDB/1KC0
  • PDB/1KC1
  • PDB/1KC3