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| - | {{STRUCTURE_1ek6| PDB=1ek6 | SCENE= }} | |
| - | ===STRUCTURE OF HUMAN UDP-GALACTOSE 4-EPIMERASE COMPLEXED WITH NADH AND UDP-GLUCOSE=== | |
| - | {{ABSTRACT_PUBMED_10801319}} | |
| | | | |
| - | ==Disease== | + | ==STRUCTURE OF HUMAN UDP-GALACTOSE 4-EPIMERASE COMPLEXED WITH NADH AND UDP-GLUCOSE== |
| - | [[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='1ek6' size='340' side='right'caption='[[1ek6]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1ek6]] 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=1EK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EK6 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]] 1.5Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene>, <scene name='pdbligand=TMA:TETRAMETHYLAMMONIUM+ION'>TMA</scene>, <scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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=1ek6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ek6 OCA], [https://pdbe.org/1ek6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ek6 RCSB], [https://www.ebi.ac.uk/pdbsum/1ek6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ek6 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/ek/1ek6_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=1ek6 ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | ==Function== | + | ==See Also== |
| - | [[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. | + | *[[UDP-galactose 4-epimerase|UDP-galactose 4-epimerase]] |
| - | | + | == References == |
| - | ==About this Structure==
| + | <references/> |
| - | [[1ek6]] 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=1EK6 OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:010801319</ref><references group="xtra"/><references/>
| + | |
| | [[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]]
| + | |
| Structural highlights
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.[1] [2] [3] [4] [5] [6] [7] [8]
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.
See Also
References
- ↑ Timson DJ. Functional analysis of disease-causing mutations in human UDP-galactose 4-epimerase. FEBS J. 2005 Dec;272(23):6170-7. PMID:16302980 doi:10.1111/j.1742-4658.2005.05017.x
- ↑ Maceratesi P, Daude N, Dallapiccola B, Novelli G, Allen R, Okano Y, Reichardt J. Human UDP-galactose 4' epimerase (GALE) gene and identification of five missense mutations in patients with epimerase-deficiency galactosemia. Mol Genet Metab. 1998 Jan;63(1):26-30. PMID:9538513 doi:S1096-7192(97)92645-7
- ↑ Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM. Molecular basis for severe epimerase deficiency galactosemia. X-ray structure of the human V94m-substituted UDP-galactose 4-epimerase. J Biol Chem. 2001 Jun 8;276(23):20617-23. Epub 2001 Mar 7. PMID:11279193 doi:10.1074/jbc.M101304200
- ↑ Quimby BB, Alano A, Almashanu S, DeSandro AM, Cowan TM, Fridovich-Keil JL. Characterization of two mutations associated with epimerase-deficiency galactosemia, by use of a yeast expression system for human UDP-galactose-4-epimerase. Am J Hum Genet. 1997 Sep;61(3):590-8. PMID:9326324 doi:S0002-9297(07)64322-5
- ↑ Wohlers TM, Christacos NC, Harreman MT, Fridovich-Keil JL. Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with generalized epimerase-deficiency galactosemia. Am J Hum Genet. 1999 Feb;64(2):462-70. PMID:9973283 doi:S0002-9297(07)61751-0
- ↑ Henderson JM, Huguenin SM, Cowan TM, Fridovich-Keil JL. A PCR-based method for detecting known mutations in the human UDP galactose-4'-epimerase gene associated with epimerase-deficiency galactosemia. Clin Genet. 2001 Nov;60(5):350-5. PMID:11903335
- ↑ Park HD, Park KU, Kim JQ, Shin CH, Yang SW, Lee DH, Song YH, Song J. The molecular basis of UDP-galactose-4-epimerase (GALE) deficiency galactosemia in Korean patients. Genet Med. 2005 Nov-Dec;7(9):646-9. PMID:16301867 doi:10.109701.gim.0000194023.27802.2d
- ↑ Wasilenko J, Lucas ME, Thoden JB, Holden HM, Fridovich-Keil JL. Functional characterization of the K257R and G319E-hGALE alleles found in patients with ostensibly peripheral epimerase deficiency galactosemia. Mol Genet Metab. 2005 Jan;84(1):32-8. PMID:15639193 doi:S1096-7192(04)00242-2
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