6b9p: Difference between revisions
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==Structure of GH 38 Jack Bean alpha-mannosidase in complex with a 36-valent iminosugar cluster inhibitor== | |||
<StructureSection load='6b9p' size='340' side='right'caption='[[6b9p]], [[Resolution|resolution]] 2.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6b9p]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Canavalia_ensiformis Canavalia ensiformis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B9P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B9P 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]] 1.996Å</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=D0J:(2R,3R,4R,5S)-2-(hydroxymethyl)-1-{9-[4-(methoxymethyl)-1H-1,2,3-triazol-1-yl]nonyl}piperidine-3,4,5-triol'>D0J</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6b9p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b9p OCA], [https://pdbe.org/6b9p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b9p RCSB], [https://www.ebi.ac.uk/pdbsum/6b9p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b9p ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MANA_CANEN MANA_CANEN] Liberates mannose from p-nitrophenyl-alpha-D-mannoside (PubMed:1156387, PubMed:12325362, PubMed:4973951). Liberates mannose from further alpha-D-mannosides including methyl-, benzyl-alpha-D-mannoside, 1-6-linked di-, tri- and tetrasaccharides of alpha-D-mannose and mannosyl-rhamnose (PubMed:12325362). Liberates mannose from various glycoproteins like ovalbumin and ovomucoid (PubMed:12325362, PubMed:5145). Does not hydrolyze beta-D-mannosides (PubMed:12325362). Has glycosyltransferase activity, forming disaccharides from mannose and lyxose but not from glucose, galactose, ribose, xylose or arabinose (PubMed:12325362).<ref>PMID:1156387</ref> <ref>PMID:12325362</ref> <ref>PMID:4973951</ref> <ref>PMID:5145</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Multivalent design of glycosidase inhibitors is a promising strategy for the treatment of diseases involving enzymatic hydrolysis of glycosidic bonds in carbohydrates. An essential prerequisite for successful applications is the atomic-level understanding of how outstanding binding enhancement occurs with multivalent inhibitors. Herein we report the first high-resolution crystal structures of the Jack bean alpha-mannosidase (JBalpha-man) in apo and inhibited states. The three-dimensional structure of JBalpha-man in complex with the multimeric cyclopeptoid-based inhibitor displaying the largest binding enhancements reported so far provides decisive insight into the molecular mechanisms underlying multivalent effects in glycosidase inhibition. | |||
Structural Basis of Outstanding Multivalent Effects in Jack Bean alpha-Mannosidase Inhibition.,Howard E, Cousido-Siah A, Lepage ML, Schneider JP, Bodlenner A, Mitschler A, Meli A, Izzo I, Alvarez HA, Podjarny A, Compain P Angew Chem Int Ed Engl. 2018 Jul 2;57(27):8002-8006. doi: 10.1002/anie.201801202., Epub 2018 Jun 6. PMID:29722924<ref>PMID:29722924</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6b9p" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: De Riccardis | *[[Mannosidase 3D structures|Mannosidase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Canavalia ensiformis]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bodlenner A]] | |||
[[Category: Compain P]] | |||
[[Category: Cousido-Siah A]] | |||
[[Category: De Riccardis F]] | |||
[[Category: Howard E]] | |||
[[Category: Izzo I]] | |||
[[Category: Lepage M]] | |||
[[Category: Meli A]] | |||
[[Category: Mitschler A]] | |||
[[Category: Podjarny A]] | |||