View source for 7zll


==Catalytic domain of UDP-Glucose Glycoprotein Glucosyltransferase from Chaetomium thermophilum in complex with the 5-[(morpholin-4-yl)methyl]quinolin-8-ol inhibitor==
<StructureSection load='7zll' size='340' side='right'caption='[[7zll]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zll]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum Chaetomium thermophilum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZLL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZLL 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]] 1.649&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JM3:5-(morpholin-4-ylmethyl)quinolin-8-ol'>JM3</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7zll FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zll OCA], [https://pdbe.org/7zll PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zll RCSB], [https://www.ebi.ac.uk/pdbsum/7zll PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zll ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G0SB58_CHATD G0SB58_CHATD] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Misfolded glycoprotein recognition and endoplasmic reticulum (ER) retention are mediated by the ER glycoprotein folding quality control (ERQC) checkpoint enzyme, UDP-glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. The small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds a CtUGGT(GT24) "WY" conserved surface motif conserved across UGGTs but not present in other GT24 family glycosyltransferases. 5M-8OH-Q has a 47 muM binding affinity for CtUGGT(GT24)in vitro as measured by ligand-enhanced fluorescence. In cellula, 5M-8OH-Q inhibits both human UGGT isoforms at concentrations higher than 750 muM. 5M-8OH-Q binding to CtUGGT(GT24) appears to be mutually exclusive to M5-9 glycan binding in an in vitro competition experiment. A medicinal program based on 5M-8OH-Q will yield the next generation of UGGT inhibitors.

A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint.,Guay KP, Ibba R, Kiappes JL, Vasiljevic S, Boni F, De Benedictis M, Zeni I, Le Cornu JD, Hensen M, Chandran AV, Kantsadi AL, Caputo AT, Blanco Capurro JI, Bayo Y, Hill JC, Hudson K, Lia A, Brun J, Withers SG, Marti M, Biasini E, Santino A, De Rosa M, Milani M, Modenutti CP, Hebert DN, Zitzmann N, Roversi P iScience. 2023 Sep 20;26(10):107919. doi: 10.1016/j.isci.2023.107919. eCollection , 2023 Oct 20. PMID:37822503<ref>PMID:37822503</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zll" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Chaetomium thermophilum]]
[[Category: Large Structures]]
[[Category: Bayo Y]]
[[Category: Chandran AV]]
[[Category: Kantsadi AL]]
[[Category: Roversi P]]
[[Category: Zitzmann N]]