View source for 5ief


==Murine endoplasmic reticulum alpha-glucosidase II with N-butyl-1-deoxynojirimycin==
<StructureSection load='5ief' size='340' side='right'caption='[[5ief]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5ief]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IEF 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]] 2.38&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NBV:(2R,3R,4R,5S)-1-BUTYL-2-(HYDROXYMETHYL)PIPERIDINE-3,4,5-TRIOL'>NBV</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</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=5ief FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ief OCA], [https://pdbe.org/5ief PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ief RCSB], [https://www.ebi.ac.uk/pdbsum/5ief PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ief ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GANAB_MOUSE GANAB_MOUSE] Cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins.
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== Publication Abstract from PubMed ==
The biosynthesis of enveloped viruses depends heavily on the host cell endoplasmic reticulum (ER) glycoprotein quality control (QC) machinery. This dependency exceeds the dependency of host glycoproteins, offering a window for the targeting of ERQC for the development of broad-spectrum antivirals. We determined small-angle X-ray scattering (SAXS) and crystal structures of the main ERQC enzyme, ER alpha-glucosidase II (alpha-GluII; from mouse), alone and in complex with key ligands of its catalytic cycle and antiviral iminosugars, including two that are in clinical trials for the treatment of dengue fever. The SAXS data capture the enzyme's quaternary structure and suggest a conformational rearrangement is needed for the simultaneous binding of a monoglucosylated glycan to both subunits. The X-ray structures with key catalytic cycle intermediates highlight that an insertion between the +1 and +2 subsites contributes to the enzyme's activity and substrate specificity, and reveal that the presence of d-mannose at the +1 subsite renders the acid catalyst less efficient during the cleavage of the monoglucosylated substrate. The complexes with iminosugar antivirals suggest that inhibitors targeting a conserved ring of aromatic residues between the alpha-GluII +1 and +2 subsites would have increased potency and selectivity, thus providing a template for further rational drug design.

Structures of mammalian ER alpha-glucosidase II capture the binding modes of broad-spectrum iminosugar antivirals.,Caputo AT, Alonzi DS, Marti L, Reca IB, Kiappes JL, Struwe WB, Cross A, Basu S, Lowe ED, Darlot B, Santino A, Roversi P, Zitzmann N Proc Natl Acad Sci U S A. 2016 Jul 26. pii: 201604463. PMID:27462106<ref>PMID:27462106</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5ief" style="background-color:#fffaf0;"></div>

==See Also==
*[[Alpha-glucosidase 3D structures|Alpha-glucosidase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Alonzi DS]]
[[Category: Caputo AT]]
[[Category: Kiappes JL]]
[[Category: Roversi P]]
[[Category: Zitzmann N]]