1hzj

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{{STRUCTURE_1hzj| PDB=1hzj | SCENE= }}
{{STRUCTURE_1hzj| PDB=1hzj | SCENE= }}
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'''HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE'''
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===HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE===
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==Overview==
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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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(as it appears on PubMed at http://www.pubmed.gov), where 11279032 is the PubMed ID number.
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{{ABSTRACT_PUBMED_11279032}}
==About this Structure==
==About this Structure==
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[[Category: Galactosemia]]
[[Category: Galactosemia]]
[[Category: Short-chain dehydrogenase]]
[[Category: Short-chain dehydrogenase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:23:59 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 10:11:04 2008''

Revision as of 07:11, 1 July 2008

Image:1hzj.png

Template:STRUCTURE 1hzj

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

Template:ABSTRACT PUBMED 11279032

About this Structure

1HZJ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

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

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