High-resolution crystal structure of Trypanosoma brucei UDP-galactose 4'-epimerase: a potential target for structure-based development of novel trypanocides

Mol Biochem Parasitol. 2003 Feb;126(2):173-80. doi: 10.1016/s0166-6851(02)00243-8.


The crystal structure of UDP-galactose 4'-epimerase from the protozoan parasite Trypanosoma brucei in complex with the cofactor NAD(+) and a fragment of the substrates, UDP, has been determined at 2.0 A resolution (1 A = 0.1 nm). This enzyme, recently proven to be essential for this pathogenic parasite, shares 33% sequence identity with the corresponding enzyme in the human host. Structural comparisons indicate that many of the protein-ligand interactions are conserved between the two enzymes. However, in the UDP-binding pocket there is a non-conservative substitution from Gly237 in the human enzyme to Cys266 in the T. brucei enzyme. Such a significant difference could be exploited by the structure-based design of selective inhibitors using the structure of the trypanosomatid enzyme as a template.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray / methods
  • Drug Design
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Sequence Alignment
  • Trypanocidal Agents / chemical synthesis*
  • Trypanosoma brucei brucei / enzymology*
  • UDPglucose 4-Epimerase / chemistry*


  • Trypanocidal Agents
  • UDPglucose 4-Epimerase

Associated data

  • PDB/1GY8
  • PDB/R1GY85F