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==Structure of the catalytic domain of the Bacillus circulans alpha-1,6 Mannanase in complex with an alpha-1,6-alpha-manno-cyclophellitol trisaccharide inhibitor== | ==Structure of the catalytic domain of the Bacillus circulans alpha-1,6 Mannanase in complex with an alpha-1,6-alpha-manno-cyclophellitol trisaccharide inhibitor== | ||
<StructureSection load='7nl5' size='340' side='right'caption='[[7nl5]]' scene=''> | <StructureSection load='7nl5' size='340' side='right'caption='[[7nl5]], [[Resolution|resolution]] 1.40Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NL5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NL5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7nl5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7NL5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7NL5 FirstGlance]. <br> | ||
</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=7nl5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nl5 OCA], [https://pdbe.org/7nl5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nl5 RCSB], [https://www.ebi.ac.uk/pdbsum/7nl5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nl5 ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UKQ:(1R,6S)-5beta-(Hydroxymethyl)-7-oxabicyclo[4.1.0]heptane-2beta,3beta,4alpha-triol'>UKQ</scene>, <scene name='pdbligand=UKT:(1R,2R,3R,4S,5R)-4-(hydroxymethyl)cyclohexane-1,2,3,5-tetrol'>UKT</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=7nl5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7nl5 OCA], [https://pdbe.org/7nl5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7nl5 RCSB], [https://www.ebi.ac.uk/pdbsum/7nl5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7nl5 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
There is a vast genomic resource for enzymes active on carbohydrates. Lagging far behind, however, are functional chemical tools for the rapid characterization of carbohydrate-active enzymes. Activity-based probes (ABPs) offer one chemical solution to these issues with ABPs based upon cyclophellitol epoxide and aziridine covalent and irreversible inhibitors representing a potent and widespread approach. Such inhibitors for enzymes active on polysaccharides are potentially limited by the requirement for several glycosidic bonds, themselves substrates for the enzyme targets. Here we show that non-hydrolysable trisaccharide can be synthesized and applied even to enzymes with challenging subsite requirements. We find that incorporation of carbasugar moieties, which we accomplished by cuprate-assisted regioselective trans-diaxial epoxide opening of carba-mannal we synthesised for this purpose, yields inactivators that act as powerful activity-based inhibitors for a-1,6 endo-mannanases. 3-D structures at 1.35 - 1.47 A resolutions confirm the design rationale and binding to the enzymatic nucleophile. Carbasugar oligosaccharide cyclophellitols offer a powerful new approach for the design of robust endoglycosidase inhibitors, while the synthesis procedures presented here should allow adaptation towards activity-based endoglycosidase probes as well as configurational isosteres targeting other endoglycosidase families. | |||
The Development of Non-Hydrolysable Oligosaccharide Activity-Based Inactivators for Endoglycanases: A Case Study on a-1,6 Mannanases.,Overkleeft HS, Schroder S, Offen W, Males A, Jin Y, de Boer C, Enotarpi J, van der Marel G, Florea B, Codee J, Davies G Chemistry. 2021 Apr 20. doi: 10.1002/chem.202101255. PMID:33878235<ref>PMID:33878235</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7nl5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Boer, C De]] | ||
[[Category: | [[Category: Codee, J D.C]] | ||
[[Category: | [[Category: Davies, G J]] | ||
[[Category: Enotarpi J]] | [[Category: Enotarpi, J]] | ||
[[Category: Florea | [[Category: Florea, B I]] | ||
[[Category: Jin Y]] | [[Category: Jin, Y]] | ||
[[Category: Males A]] | [[Category: Males, A]] | ||
[[Category: Marino L]] | [[Category: Marel, G A.van der]] | ||
[[Category: Offen | [[Category: Marino, L]] | ||
[[Category: Overkleeft | [[Category: Offen, W A]] | ||
[[Category: Schroeder S]] | [[Category: Overkleeft, H S]] | ||
[[Category: | [[Category: Schroeder, S]] | ||
[[Category: Cyclophellitol]] | |||
[[Category: Epoxide]] | |||
[[Category: Hydrolase]] | |||
[[Category: Mannanase]] | |||