View source for 5in3


==Crystal structure of glucose-1-phosphate bound nucleotidylated human galactose-1-phosphate uridylyltransferase==
<StructureSection load='5in3' size='340' side='right'caption='[[5in3]], [[Resolution|resolution]] 1.73&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5in3]] 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=5IN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IN3 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]] 1.73&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=G1P:ALPHA-D-GLUCOSE-1-PHOSPHATE'>G1P</scene>, <scene name='pdbligand=H2U:5,6-DIHYDROURIDINE-5-MONOPHOSPHATE'>H2U</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5in3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5in3 OCA], [https://pdbe.org/5in3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5in3 RCSB], [https://www.ebi.ac.uk/pdbsum/5in3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5in3 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GALT_HUMAN GALT_HUMAN] Classic galactosemia. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/GALT_HUMAN GALT_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Classic galactosemia is a potentially lethal disease caused by the dysfunction of galactose 1-phosphate uridylyltransferase (GALT). Over 300 disease-associated GALT mutations have been reported, with the majority being missense changes, although a better understanding of their underlying molecular effects has been hindered by the lack of structural information for the human enzyme. Here, we present the 1.9 A resolution crystal structure of human GALT (hGALT) ternary complex, revealing a homodimer arrangement that contains a covalent uridylylated intermediate and glucose-1-phosphate in the active site, as well as a structural zinc-binding site, per monomer. hGALT reveals significant structural differences from bacterial GALT homologues in metal ligation and dimer interactions, and therefore is a zbetter model for understanding the molecular consequences of disease mutations. Both uridylylation and zinc binding influence the stability and aggregation tendency of hGALT. This has implications for disease-associated variants where p.Gln188Arg, the most commonly detected, increases the rate of aggregation in the absence of zinc likely due to its reduced ability to form the uridylylated intermediate. As such our structure serves as a template in the future design of pharmacological chaperone therapies and opens new concepts about the roles of metal binding and activity in protein misfolding by disease-associated mutants.

Molecular basis of classic galactosemia from the structure of human galactose 1-phosphate uridylyltransferase.,McCorvie TJ, Kopec J, Pey AL, Fitzpatrick F, Patel D, Chalk R, Shrestha L, Yue WW Hum Mol Genet. 2016 Mar 22. pii: ddw091. PMID:27005423<ref>PMID:27005423</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5in3" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrowsmith C]]
[[Category: Bountra C]]
[[Category: Burgess-Brown N]]
[[Category: Chalk R]]
[[Category: Edwards A]]
[[Category: Fitzpatrick F]]
[[Category: Kopec J]]
[[Category: McCorvie T]]
[[Category: Patel D]]
[[Category: Shrestha L]]
[[Category: Tallant C]]
[[Category: Velupillai S]]
[[Category: Yue WW]]
[[Category: Von Delft F]]