This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1hzj

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:18, 9 August 2023) (edit) (undo)
 
(7 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_1hzj| PDB=1hzj | SCENE= }}
 
-
===HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE===
 
-
{{ABSTRACT_PUBMED_11279032}}
 
-
==Disease==
+
==HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE==
-
[[http://www.uniprot.org/uniprot/GALE_HUMAN GALE_HUMAN]] Defects in GALE are the cause of epimerase-deficiency galactosemia (EDG) [MIM:[http://omim.org/entry/230350 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.<ref>PMID:16302980</ref><ref>PMID:9538513</ref><ref>PMID:11279193</ref><ref>PMID:9326324</ref><ref>PMID:9973283</ref><ref>PMID:11903335</ref><ref>PMID:16301867</ref><ref>PMID:15639193</ref>
+
<StructureSection load='1hzj' size='340' side='right'caption='[[1hzj]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1hzj]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HZJ FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hzj OCA], [https://pdbe.org/1hzj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hzj RCSB], [https://www.ebi.ac.uk/pdbsum/1hzj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hzj ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/GALE_HUMAN GALE_HUMAN] Defects in GALE are the cause of epimerase-deficiency galactosemia (EDG) [MIM:[https://omim.org/entry/230350 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.<ref>PMID:16302980</ref> <ref>PMID:9538513</ref> <ref>PMID:11279193</ref> <ref>PMID:9326324</ref> <ref>PMID:9973283</ref> <ref>PMID:11903335</ref> <ref>PMID:16301867</ref> <ref>PMID:15639193</ref>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/GALE_HUMAN 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 ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hz/1hzj_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hzj ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== 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.
-
==Function==
+
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<ref>PMID:11279032</ref>
-
[[http://www.uniprot.org/uniprot/GALE_HUMAN 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.
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[1hzj]] is a 2 chain structure with 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].
+
</div>
 +
<div class="pdbe-citations 1hzj" style="background-color:#fffaf0;"></div>
-
==Reference==
+
==See Also==
-
<ref group="xtra">PMID:011279032</ref><ref group="xtra">PMID:015799708</ref><references group="xtra"/><references/>
+
*[[UDP-galactose 4-epimerase|UDP-galactose 4-epimerase]]
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: UDP-glucose 4-epimerase]]
+
[[Category: Large Structures]]
-
[[Category: Fridovich-Keil, J L.]]
+
[[Category: Fridovich-Keil JL]]
-
[[Category: Holden, H M.]]
+
[[Category: Holden HM]]
-
[[Category: Thoden, J B.]]
+
[[Category: Thoden JB]]
-
[[Category: Wohlers, T M.]]
+
[[Category: Wohlers TM]]
-
[[Category: Epimerase]]
+
-
[[Category: Galactosemia]]
+
-
[[Category: Isomerase]]
+
-
[[Category: Short-chain dehydrogenase]]
+

Current revision

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

PDB ID 1hzj

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hzj"
Personal tools