11li: Difference between revisions
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==OgOGA IN COMPLEX WITH LIGAND 24== | |||
<StructureSection load='11li' size='340' side='right'caption='[[11li]], [[Resolution|resolution]] 1.53Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[11li]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oceanicola_granulosus_HTCC2516 Oceanicola granulosus HTCC2516]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=11LI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=11LI 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]] 1.53Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DE3:N,N-dimethyl-2-(4-{[4-methyl-2-(propan-2-yl)pyridin-3-yl]amino}-1H-pyrrolo[3,2-c]pyridin-1-yl)acetamide'>A1DE3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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=11li FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=11li OCA], [https://pdbe.org/11li PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=11li RCSB], [https://www.ebi.ac.uk/pdbsum/11li PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=11li ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/OGA_OCEGH OGA_OCEGH] Cleaves GlcNAc from O-glycosylated proteins. Can use p-nitrophenyl-beta-GlcNAc and 4-methylumbelliferone-GlcNAc as substrate (in vitro).<ref>PMID:20863279</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid-beta plaque accumulation and intracellular tau neurofibrillary tangles, with tau pathology correlating more closely with cognitive decline. Modulation of tau phosphorylation through the regulation of O-GlcNAcylation, a post-translational modification controlled by O-GlcNAcase (OGA), represents a promising therapeutic strategy. In this study, we report the optimization of a pyrimidine hit identified by high-throughput screening, leading to the discovery and optimization of a novel series of 5-azaindole-based OGA inhibitors. From this series, compound 24 was identified as an in vivo tool candidate that demonstrated a favorable pharmacokinetic profile and measurable brain exposure. Pharmacodynamic studies in murine models demonstrated that compound 24 induced a significant and transient elevation of brain O-GlcNAcylation levels, confirming the in vivo target engagement. These findings underscore the potential of 5-azaindole-based OGA inhibitors as a novel validated chemotype for modulation of O-GlcNAcylation. | |||
Discovery of 5âAzaindole Inhibitors of OâGlcNAcase for the Treatment of Alzheimer's Disease and Related Tauopathies.,Bouton J, Bretteville A, Tresadern G, Shaffer P, Austin N, Buijnsters P, Cedervall EP, Darville N, Fonteyn I, Leenaerts J, Lamenca CM, Mertens L, Peeters D, Velter AI, Roosbroeck YV, Ebneth A, Bartolome JM, Trabanco AA, Oehlrich D ACS Med Chem Lett. 2026 Apr 23;17(5):1096-1105. doi: , 10.1021/acsmedchemlett.6c00017. eCollection 2026 May 14. PMID:42157845<ref>PMID:42157845</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Shaffer | <div class="pdbe-citations 11li" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Oceanicola granulosus HTCC2516]] | |||
[[Category: Shaffer PL]] | |||
