This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
7mfl
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 7mfl is ON HOLD until Apr 09 2023 Authors: Boraston, A.B. Description: Structure of the Clostridium perfringens GH89 in complex with beta-HNJNAc [[...) |
|||
| (3 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the Clostridium perfringens GH89 in complex with beta-HNJNAc== | |
| + | <StructureSection load='7mfl' size='340' side='right'caption='[[7mfl]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7mfl]] 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=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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</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='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> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Boraston | + | <div class="pdbe-citations 7mfl" style="background-color:#fffaf0;"></div> |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Clostridium perfringens ATCC 13124]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Boraston AB]] | ||
Current revision
Structure of the Clostridium perfringens GH89 in complex with beta-HNJNAc
| |||||||||||
