Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site

J Biol Chem. 2001 May 4;276(18):15131-6. doi: 10.1074/jbc.M100220200. Epub 2001 Jan 26.


UDP-galactose 4-epimerase catalyzes the interconversion of UDP-galactose and UDP-glucose during normal galactose metabolism. One of the key structural features in the proposed reaction mechanism for the enzyme is the rotation of a 4'-ketopyranose intermediate within the active site pocket. Recently, the three-dimensional structure of the human enzyme with bound NADH and UDP-glucose was determined. Unlike that observed for the protein isolated from Escherichia coli, the human enzyme can also turn over UDP-GlcNAc to UDP-GalNAc and vice versa. Here we describe the three-dimensional structure of human epimerase complexed with NADH and UDP-GlcNAc. To accommodate the additional N-acetyl group at the C2 position of the sugar, the side chain of Asn-207 rotates toward the interior of the protein and interacts with Glu-199. Strikingly, in the human enzyme, the structural equivalent of Tyr-299 in the E. coli protein is replaced with a cysteine residue (Cys-307) and the active site volume for the human protein is calculated to be approximately 15% larger than that observed for the bacterial epimerase. This combination of a larger active site cavity and amino acid residue replacement most likely accounts for the inability of the E. coli enzyme to interconvert UDP-GlcNAc and UDP-GalNAc.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Escherichia coli / genetics
  • Humans
  • Models, Molecular
  • NAD / metabolism
  • Protein Conformation
  • UDPglucose 4-Epimerase / chemistry
  • UDPglucose 4-Epimerase / genetics
  • UDPglucose 4-Epimerase / metabolism*
  • Uridine Diphosphate Galactose / metabolism
  • Uridine Diphosphate Glucose / metabolism
  • Uridine Diphosphate N-Acetylglucosamine / metabolism*


  • NAD
  • Uridine Diphosphate Galactose
  • Uridine Diphosphate N-Acetylglucosamine
  • UDPglucose 4-Epimerase
  • Uridine Diphosphate Glucose

Associated data

  • PDB/1HZJ