7mfl: Difference between revisions
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==Structure of the Clostridium perfringens GH89 in complex with beta-HNJNAc== | ==Structure of the Clostridium perfringens GH89 in complex with beta-HNJNAc== | ||
<StructureSection load='7mfl' size='340' side='right'caption='[[7mfl]]' scene=''> | <StructureSection load='7mfl' size='340' side='right'caption='[[7mfl]], [[Resolution|resolution]] 2.00Å' 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=7MFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MFL FirstGlance]. <br> | <table><tr><td colspan='2'>[[7mfl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clop1 Clop1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MFL 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=7mfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mfl OCA], [https://pdbe.org/7mfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mfl RCSB], [https://www.ebi.ac.uk/pdbsum/7mfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mfl 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=Z8V:N-[(2R,3S,4R,5R,6R)-4,5-dihydroxy-2,6-bis(hydroxymethyl)piperidin-3-yl]acetamide'>Z8V</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CPF_0859 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=195103 CLOP1])</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=7mfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mfl OCA], [https://pdbe.org/7mfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mfl RCSB], [https://www.ebi.ac.uk/pdbsum/7mfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mfl ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mucopolysaccharidosis type IIIB is a devastating neurological disease caused by a lack of the lysosomal enzyme, alpha-N-acetylglucosaminidase (NAGLU), leading to a toxic accumulation of heparan sulfate. Herein we explored a pharmacological chaperone approach to enhance the residual activity of NAGLU in patient fibroblasts. Capitalizing on the three-dimensional structures of two modest homoiminosugar-based NAGLU inhibitors in complex with bacterial homolog of NAGLU, CpGH89, we have synthesized a library of 17 iminosugar C-glycosides mimicking N-acetyl-D-glucosamine and bearing various pseudo-anomeric substituents of both alpha- and beta-configuration. Elaboration of the aglycon moiety results in low micromolar selective inhibitors of human recombinant NAGLU, but surprisingly it is the non-functionalized and wrongly configured beta-homoiminosugar that was proved to act as the most promising pharmacological chaperone, promoting a 2.4 fold activity enhancement of mutant NAGLU at its optimal concentration. | |||
Iminosugar C-Glycosides Work as Pharmacological Chaperones of NAGLU, a Glycosidase Involved in MPS IIIB Rare Disease*.,Zhu S, Jagadeesh Y, Tran AT, Imaeda S, Boraston A, Alonzi DS, Poveda A, Zhang Y, Desire J, Charollais-Thoenig J, Demotz S, Kato A, Butters TD, Jimenez-Barbero J, Sollogoub M, Bleriot Y Chemistry. 2021 Jun 9. doi: 10.1002/chem.202101408. PMID:34106504<ref>PMID:34106504</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7mfl" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Clop1]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Boraston | [[Category: Boraston, A B]] | ||
[[Category: Clostridium perfringen]] | |||
[[Category: Gh89]] | |||
[[Category: Glycoside hydrolase]] | |||
[[Category: Hydrolase-inhibitor complex]] | |||
[[Category: Inhibitor]] | |||
[[Category: Mps iiib]] | |||
[[Category: Naglu]] | |||
Revision as of 10:36, 4 August 2021
Structure of the Clostridium perfringens GH89 in complex with beta-HNJNAc
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