1HZJ

HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE

Summary for 1HZJ

• Entry DOI: 10.2210/pdb1hzj/pdb
• Descriptor: UDP-GALACTOSE 4-EPIMERASE, CHLORIDE ION, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: epimerase, short-chain dehydrogenase, galactosemia, isomerase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 79377.54

Authors

Thoden, J.B.,Wohlers, T.M.,Fridovich-Keil, J.L.,Holden, H.M. (deposition date: 2001-01-25, release date: 2001-05-09, Last modification date: 2023-08-09)

Primary citation

Thoden, J.B.,Wohlers, T.M.,Fridovich-Keil, J.L.,Holden, H.M.
Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site.
J.Biol.Chem., 276:15131-15136, 2001

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.

PubMed: 11279032
DOI: 10.1074/jbc.M100220200

Experimental method

X-RAY DIFFRACTION (1.5 Å)