View source for 7mfk


==Structure of the Clostridium perfringens GH89 in complex with alpha-HNJNAc==
<StructureSection load='7mfk' size='340' side='right'caption='[[7mfk]], [[Resolution|resolution]] 2.13&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7mfk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens_ATCC_13124 Clostridium perfringens ATCC 13124]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MFK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MFK 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]] 2.13&#8491;</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=Z7S:N-[(2S,3S,4R,5R,6R)-4,5-dihydroxy-2,6-bis(hydroxymethyl)piperidin-3-yl]acetamide'>Z7S</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=7mfk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mfk OCA], [https://pdbe.org/7mfk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mfk RCSB], [https://www.ebi.ac.uk/pdbsum/7mfk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mfk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H2YU91_CLOP1 A0A0H2YU91_CLOP1] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7mfk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Clostridium perfringens ATCC 13124]]
[[Category: Large Structures]]
[[Category: Boraston AB]]