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| | <StructureSection load='2ow6' size='340' side='right'caption='[[2ow6]], [[Resolution|resolution]] 1.19Å' scene=''> | | <StructureSection load='2ow6' size='340' side='right'caption='[[2ow6]], [[Resolution|resolution]] 1.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ow6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OW6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ow6]] 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=2OW6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OW6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NK1:(1R,5S,6S,7R,8S)-1-THIONIABICYCLO[4.3.0]NONAN-5,7,8-TRIOL'>NK1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 1.19Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1hty|1hty]], [[1hww|1hww]], [[1hxk|1hxk]], [[1ps3|1ps3]], [[1qwn|1qwn]], [[1qwu|1qwu]], [[1qx1|1qx1]], [[1r33|1r33]], [[1r34|1r34]], [[1tqs|1tqs]], [[1tqt|1tqt]], [[1tqu|1tqu]], [[1tqv|1tqv]], [[1tqw|1tqw]], [[2alw|2alw]], [[2f18|2f18]], [[2f1a|2f1a]], [[2f1b|2f1b]], [[2f7o|2f7o]], [[2f7q|2f7q]], [[2f7r|2f7r]], [[2fyv|2fyv]], [[2ow7|2ow7]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NK1:(1R,5S,6S,7R,8S)-1-THIONIABICYCLO[4.3.0]NONAN-5,7,8-TRIOL'>NK1</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alpha-Man-II ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Mannosyl-oligosaccharide_1,3-1,6-alpha-mannosidase Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.114 3.2.1.114] </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=2ow6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ow6 OCA], [https://pdbe.org/2ow6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ow6 RCSB], [https://www.ebi.ac.uk/pdbsum/2ow6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ow6 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=2ow6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ow6 OCA], [https://pdbe.org/2ow6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ow6 RCSB], [https://www.ebi.ac.uk/pdbsum/2ow6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ow6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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).
| + | [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). |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Mannosyl-oligosaccharide 1,3-1,6-alpha-mannosidase]]
| + | [[Category: Kuntz DA]] |
| - | [[Category: Kuntz, D A]] | + | |
| - | [[Category: Glycosyl hydrolase family 38]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
2ow6 is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.19Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
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).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Retaining glycosidases operate by a two-step catalytic mechanism in which the transition states are characterized by buildup of a partial positive charge at the anomeric center. Sulfonium-ion analogues of the naturally occurring glycosidase inhibitors, swainsonine and 8-epi-lentiginosine, in which the bridgehead nitrogen atom is replaced by a sulfonium-ion, were synthesized in order to test the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor. Initial prediction based on computational docking indicated three plausible binding modes to Drosophila Golgi alpha-mannosidase II (dGMII), the most likely being close to that of swainsonine. Observation of the binding of di-epi-thioswainsonine and 8-epi-thiolentiginosine to dGMII from crystallographic data, however, revealed an orientation different from swainsonine in the active site. Screening these two compounds against dGMII shows that they are inhibitors with IC(50) values of 2.0 and 0.014 mM, respectively. This dramatic difference in affinity between the two compounds, which differ by only one hydroxyl group, is rationalized in terms of bound water molecules and the water molecule substructure in the active site, as identified by comparison of high resolution X-ray crystal structures of several dGMII-inhibitor complexes. Proteins 2007. (c) 2007 Wiley-Liss, Inc.
Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine to Drosophila Golgi alpha-mannosidase II: The role of water in inhibitor binding.,Kumar NS, Kuntz DA, Wen X, Pinto BM, Rose DR Proteins. 2007 Dec 12;. PMID:18076078[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kumar NS, Kuntz DA, Wen X, Pinto BM, Rose DR. Binding of sulfonium-ion analogues of di-epi-swainsonine and 8-epi-lentiginosine to Drosophila Golgi alpha-mannosidase II: The role of water in inhibitor binding. Proteins. 2007 Dec 12;. PMID:18076078 doi:http://dx.doi.org/10.1002/prot.21850
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