1hzj

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

spinqualitylabelsall models 1hzj, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1hzj is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.5Å Ligands: CL, MG, NAD, UD1 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GALE_HUMAN Defects in GALE are the cause of epimerase-deficiency galactosemia (EDG) [MIM:230350; also known as galactosemia type 3. Clinical features include early-onset cataracts, liver damage, deafness and mental retardation. There are two clinically distinct forms of EDG. (1) A benign, or 'peripheral' form with no detectable GALE activity in red blood cells and characterized by mild symptoms. Some patients may suffer no symptoms beyond raised levels of galactose-1-phosphate in the blood. (2) A much rarer 'generalized' form with undetectable levels of GALE activity in all tissues and resulting in severe features such as restricted growth and mental development. Function GALE_HUMAN Catalyzes two distinct but analogous reactions: the epimerization of UDP-glucose to UDP-galactose and the epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site.,Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM J Biol Chem. 2001 May 4;276(18):15131-6. Epub 2001 Jan 26. PMID:11279032 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also UDP-galactose 4-epimerase

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