View source for 5oxd


==Complex of a C. perfringens O-GlcNAcase with a fragment hit==
<StructureSection load='5oxd' size='340' side='right'caption='[[5oxd]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5oxd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OXD 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=B2W:5-(trifluoromethyl)-2,3-dihydro-1~{H}-1,4-diazepine'>B2W</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</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=5oxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oxd OCA], [https://pdbe.org/5oxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oxd RCSB], [https://www.ebi.ac.uk/pdbsum/5oxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oxd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/OGA_CLOP1 OGA_CLOP1] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The attachment of the sugar N-acetyl-D-glucosamine (GlcNAc) to specific serine and threonine residues on proteins is referred to as protein O-GlcNAcylation. O-GlcNAc transferase (OGT) is the enzyme responsible for carrying out the modification, while O-GlcNAcase (OGA) reverses it. Protein O-GlcNAcylation has been implicated in a wide range of cellular processes including transcription, proteostasis, and stress response. Dysregulation of O-GlcNAc has been linked to diabetes, cancer, and neurodegenerative and cardiovascular disease. OGA has been proposed to be a drug target for the treatment of Alzheimer's and cardiovascular disease given that increased O-GlcNAc levels appear to exert a protective effect. The search for specific, potent, and drug-like OGA inhibitors with bioavailability in the brain is therefore a field of active research, requiring orthogonal high-throughput assay platforms. Here, we describe the synthesis of a novel probe for use in a fluorescence polarization based assay for the discovery of inhibitors of OGA. We show that the probe is suitable for use with both human OGA, as well as the orthologous bacterial counterpart from Clostridium perfringens, CpOGA, and the lysosomal hexosaminidases HexA/B. We structurally characterize CpOGA in complex with a ligand identified from a fragment library screen using this assay. The versatile synthesis procedure could be adapted for making fluorescent probes for the assay of other glycoside hydrolases.

O-GlcNAcase Fragment Discovery with Fluorescence Polarimetry.,Borodkin VS, Rafie K, Selvan N, Aristotelous T, Navratilova I, Ferenbach AT, van Aalten DMF ACS Chem Biol. 2018 May 2. doi: 10.1021/acschembio.8b00183. PMID:29641181<ref>PMID:29641181</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5oxd" style="background-color:#fffaf0;"></div>

==See Also==
*[[O-GlcNAcase|O-GlcNAcase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium perfringens]]
[[Category: Large Structures]]
[[Category: Rafie K]]
[[Category: Van Aalten DMF]]