1wuu

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{{Seed}}
 
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[[Image:1wuu.png|left|200px]]
 
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==crystal structure of human galactokinase complexed with MgAMPPNP and galactose==
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The line below this paragraph, containing "STRUCTURE_1wuu", creates the "Structure Box" on the page.
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<StructureSection load='1wuu' size='340' side='right'caption='[[1wuu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1wuu]] is a 4 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=1WUU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WUU FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=GLA:ALPHA+D-GALACTOSE'>GLA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
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{{STRUCTURE_1wuu| PDB=1wuu | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1wuu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wuu OCA], [https://pdbe.org/1wuu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wuu RCSB], [https://www.ebi.ac.uk/pdbsum/1wuu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wuu ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN] Defects in GALK1 are the cause of galactosemia II (GALCT2) [MIM:[https://omim.org/entry/230200 230200]. Galactosemia II is an autosomal recessive deficiency characterized by congenital cataracts during infancy and presenile cataracts in the adult population. The cataracts are secondary to accumulation of galactitol in the lenses.<ref>PMID:10521295</ref> <ref>PMID:10790206</ref> <ref>PMID:11231902</ref> <ref>PMID:11139256</ref> <ref>PMID:12694189</ref> <ref>PMID:15024738</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/GALK1_HUMAN GALK1_HUMAN] Major enzyme for galactose metabolism.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wu/1wuu_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1wuu ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Galactokinase functions in the Leloir pathway for galactose metabolism by catalyzing the MgATP-dependent phosphorylation of the C-1 hydroxyl group of alpha-D-galactose. The enzyme is known to belong to the GHMP superfamily of small molecule kinases and has attracted significant research attention for well over 40 years. Approximately 20 mutations have now been identified in human galactokinase, which result in the diseased state referred to as Type II galactosemia. Here we report the three-dimensional architecture of human galactokinase with bound alpha-D-galactose and Mg-AMPPNP. The overall fold of the molecule can be described in terms of two domains with the active site wedged between them. The N-terminal domain is dominated by a six-stranded mixed beta-sheet whereas the C-terminal motif contains six alpha-helices and two layers of anti-parallel beta-sheet. Those residues specifically involved in sugar binding include Arg37, Glu43, His44, Asp46, Gly183, Asp186, and Tyr236. The C-1 hydroxyl group of alpha-D-galactose sits within 3.3 A of the gamma-phosphorus of the nucleotide and 3.4 A of the guanidinium group of Arg37. The carboxylate side chain of Asp186 lies within approximately 3.2 A of the C-2 hydroxyl group of alpha-D-galactose and the guanidinium group of Arg37. Both Arg37 and Asp186 are strictly conserved among both prokaryotic and eukaryotic galactokinases. In addition to providing molecular insight into the active site geometry of the enzyme, the model also provides a structural framework upon which to more fully understand the consequences of the those mutations known to give rise to Type II galactosemia.
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===crystal structure of human galactokinase complexed with MgAMPPNP and galactose===
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Molecular structure of human galactokinase: implications for type II galactosemia.,Thoden JB, Timson DJ, Reece RJ, Holden HM J Biol Chem. 2005 Mar 11;280(10):9662-70. Epub 2004 Dec 7. PMID:15590630<ref>PMID:15590630</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1wuu" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_15590630}}, adds the Publication Abstract to the page
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*[[Galactokinase|Galactokinase]]
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(as it appears on PubMed at http://www.pubmed.gov), where 15590630 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_15590630}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Galactokinase deficiency with cataracts OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=604313 604313]]
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==About this Structure==
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1WUU is a 4 chains structure of sequences 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=1WUU OCA].
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==Reference==
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<ref group="xtra">PMID:15590630</ref><references group="xtra"/>
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[[Category: Galactokinase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Holden, H M.]]
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[[Category: Large Structures]]
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[[Category: Reece, R J.]]
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[[Category: Holden HM]]
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[[Category: Thoden, J B.]]
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[[Category: Reece RJ]]
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[[Category: Timson, D J.]]
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[[Category: Thoden JB]]
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[[Category: Galactosemia]]
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[[Category: Timson DJ]]
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[[Category: Ghmp superfamily]]
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[[Category: Kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 13:56:32 2009''
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Current revision

crystal structure of human galactokinase complexed with MgAMPPNP and galactose

PDB ID 1wuu

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