1hzj

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[[Image:1hzj.gif|left|200px]]<br /><applet load="1hzj" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1hzj.gif|left|200px]]
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caption="1hzj, resolution 1.5&Aring;" />
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'''HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE'''<br />
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{{Structure
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|PDB= 1hzj |SIZE=350|CAPTION= <scene name='initialview01'>1hzj</scene>, resolution 1.5&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene> and <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene>
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|ACTIVITY= [http://en.wikipedia.org/wiki/UDP-glucose_4-epimerase UDP-glucose 4-epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.2 5.1.3.2]
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|GENE=
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}}
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'''HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1HZJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=UD1:'>UD1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/UDP-glucose_4-epimerase UDP-glucose 4-epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.2 5.1.3.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZJ OCA].
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1HZJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZJ OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11279032 11279032]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/11279032 11279032]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: short-chain dehydrogenase]]
[[Category: short-chain dehydrogenase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:06:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:43:43 2008''

Revision as of 09:43, 20 March 2008


PDB ID 1hzj

Drag the structure with the mouse to rotate
, resolution 1.5Å
Ligands: , , and
Activity: UDP-glucose 4-epimerase, with EC number 5.1.3.2
Coordinates: save as pdb, mmCIF, xml



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


Contents

Overview

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.

Disease

Known disease associated with this structure: Galactose epimerase deficiency OMIM:[606953]

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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