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<StructureSection load='6rs0' size='340' side='right'caption='[[6rs0]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='6rs0' size='340' side='right'caption='[[6rs0]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6rs0]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RS0 FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RS0 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]] 1.8&#8491;</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#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=KGB:(2~{S},3~{S},4~{R})-2-(hydroxymethyl)-1-(2-phenylmethoxyethyl)piperidine-3,4,5-triol'>KGB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=KGB:(2~{S},3~{S},4~{R})-2-(hydroxymethyl)-1-(2-phenylmethoxyethyl)piperidine-3,4,5-triol'>KGB</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=6rs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rs0 OCA], [https://pdbe.org/6rs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rs0 RCSB], [https://www.ebi.ac.uk/pdbsum/6rs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rs0 ProSAT]</span></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=6rs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rs0 OCA], [https://pdbe.org/6rs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rs0 RCSB], [https://www.ebi.ac.uk/pdbsum/6rs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rs0 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MAN2_DROME MAN2_DROME] Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Golgi mannosidase II (GMII) catalyzes the sequential hydrolysis of two mannosyl residues from GlcNAcMan5GlcNAc2 to produce GlcNAcMan3GlcNAc2, the precursor for all complex N-glycans, including the branched N-glycans associated with cancer. Inhibitors of GMII are potential cancer therapeutics, but their usefulness is limited by off-target effects, which produce alpha-mannosidosis-like symptoms. Despite many structural and mechanistic studies of GMII, we still lack a potent and selective inhibitor of this enzyme. Here, we synthesized manno-epi-cyclophellitol epoxide and aziridines and demonstrate their covalent modification and time-dependent inhibition of GMII. Application of fluorescent manno-epi-cyclophellitol aziridine derivatives enabled activity-based protein profiling of alpha-mannosidases from both human cell lysate and mouse tissue extracts. Synthesized probes also facilitated a fluorescence polarization-based screen for dGMII inhibitors. We identified seven previously unknown inhibitors of GMII from a library of over 350 iminosugars and investigated their binding modalities through X-ray crystallography. Our results reveal previously unobserved inhibitor binding modes and promising scaffolds for the generation of selective GMII inhibitors.
Manno-epi-cyclophellitols Enable Activity-Based Protein Profiling of Human alpha-Mannosidases and Discovery of New Golgi Mannosidase II Inhibitors.,Armstrong Z, Kuo CL, Lahav D, Liu B, Johnson R, Beenakker TJM, de Boer C, Wong CS, van Rijssel ER, Debets MF, Florea BI, Hissink C, Boot RG, Geurink PP, Ovaa H, van der Stelt M, van der Marel GM, Codee JDC, Aerts JMFG, Wu L, Overkleeft HS, Davies GJ J Am Chem Soc. 2020 Jul 29;142(30):13021-13029. doi: 10.1021/jacs.0c03880. Epub, 2020 Jul 16. PMID:32605368<ref>PMID:32605368</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6rs0" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
*[[Mannosidase 3D structures|Mannosidase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Drosophila melanogaster]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Aerts JMFG]]
[[Category: Aerts JMFG]]

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