View source for 5nv4


==UDP-Glucose Glycoprotein Glucosyltransferase from Chaetomium thermophilum double mutant D611C:G1050C==
<StructureSection load='5nv4' size='340' side='right'caption='[[5nv4]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5nv4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_var._thermophilum_DSM_1495 Chaetomium thermophilum var. thermophilum DSM 1495]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NV4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NV4 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]] 2.78&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</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=5nv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nv4 OCA], [https://pdbe.org/5nv4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nv4 RCSB], [https://www.ebi.ac.uk/pdbsum/5nv4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nv4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G0SB58_CHATD G0SB58_CHATD] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Glycoproteins traversing the eukaryotic secretory pathway begin life in the endoplasmic reticulum (ER), where their folding is surveyed by the 170-kDa UDP-glucose:glycoprotein glucosyltransferase (UGGT). The enzyme acts as the single glycoprotein folding quality control checkpoint: it selectively reglucosylates misfolded glycoproteins, promotes their association with ER lectins and associated chaperones, and prevents premature secretion from the ER. UGGT has long resisted structural determination and sequence-based domain boundary prediction. Questions remain on how this single enzyme can flag misfolded glycoproteins of different sizes and shapes for ER retention and how it can span variable distances between the site of misfold and a glucose-accepting N-linked glycan on the same glycoprotein. Here, crystal structures of a full-length eukaryotic UGGT reveal four thioredoxin-like (TRXL) domains arranged in a long arc that terminates in two beta-sandwiches tightly clasping the glucosyltransferase domain. The fold of the molecule is topologically complex, with the first beta-sandwich and the fourth TRXL domain being encoded by nonconsecutive stretches of sequence. In addition to the crystal structures, a 15-A cryo-EM reconstruction reveals interdomain flexibility of the TRXL domains. Double cysteine point mutants that engineer extra interdomain disulfide bridges rigidify the UGGT structure and exhibit impaired activity. The intrinsic flexibility of the TRXL domains of UGGT may therefore endow the enzyme with the promiscuity needed to recognize and reglucosylate its many different substrates and/or enable reglucosylation of N-linked glycans situated at variable distances from the site of misfold.

Interdomain conformational flexibility underpins the activity of UGGT, the eukaryotic glycoprotein secretion checkpoint.,Roversi P, Marti L, Caputo AT, Alonzi DS, Hill JC, Dent KC, Kumar A, Levasseur MD, Lia A, Waksman T, Basu S, Soto Albrecht Y, Qian K, McIvor JP, Lipp CB, Siliqi D, Vasiljevic S, Mohammed S, Lukacik P, Walsh MA, Santino A, Zitzmann N Proc Natl Acad Sci U S A. 2017 Jul 24. pii: 201703682. doi:, 10.1073/pnas.1703682114. PMID:28739903<ref>PMID:28739903</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5nv4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Chaetomium thermophilum var. thermophilum DSM 1495]]
[[Category: Large Structures]]
[[Category: Alonzi DS]]
[[Category: Caputo AT]]
[[Category: Hill J]]
[[Category: Roversi P]]
[[Category: Zitzmann N]]