Toward a structural understanding of the dehydratase mechanism

Structure. 2002 Jan;10(1):81-92. doi: 10.1016/s0969-2126(01)00694-3.


dTDP-D-glucose 4,6-dehydratase (RmlB) was first identified in the L-rhamnose biosynthetic pathway, where it catalyzes the conversion of dTDP-D-glucose into dTDP-4-keto-6-deoxy-D-glucose. The structures of RmlB from Salmonella enterica serovar Typhimurium in complex with substrate deoxythymidine 5'-diphospho-D-glucose (dTDP-D-glucose) and deoxythymidine 5'-diphosphate (dTDP), and RmlB from Streptococcus suis serotype 2 in complex with dTDP-D-glucose, dTDP, and deoxythymidine 5'-diphospho-D-pyrano-xylose (dTDP-xylose) have all been solved at resolutions between 1.8 A and 2.4 A. The structures show that the active sites are highly conserved. Importantly, the structures show that the active site tyrosine functions directly as the active site base, and an aspartic and glutamic acid pairing accomplishes the dehydration step of the enzyme mechanism. We conclude that the substrate is required to move within the active site to complete the catalytic cycle and that this movement is driven by the elimination of water. The results provide insight into members of the SDR superfamily.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • Glucose / analogs & derivatives
  • Glucose / metabolism
  • Hydro-Lyases / chemistry*
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Structure, Tertiary*
  • Salmonella typhimurium / enzymology*
  • Sequence Alignment
  • Streptococcus suis / enzymology*


  • Bacterial Proteins
  • Hydro-Lyases
  • dTDPglucose 4,6-dehydratase
  • Glucose

Associated data

  • PDB/1KEP
  • PDB/1KER
  • PDB/1KET
  • PDB/1KEU
  • PDB/1KEW