1HZJ

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

(2001) J Biol Chem 276: 15131-15136

• PubMed: 11279032 Search on PubMed
• DOI: https://doi.org/10.1074/jbc.M100220200
• Primary Citation of Related Structures:  
  1HZJ


• PubMed Abstract: 
  

  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.

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Organizational Affiliation: 

Department of Biochemistry, University of Wisconsin, Madison, Wisconsin 53705, USA.