6e37: Difference between revisions

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-'''Unreleased structure'''
-The entry 6e37 is ON HOLD  until Jan 15 2021
+==O-GlcNAc Transferase in complex with covalent inhibitor==
+<StructureSection load='6e37' size='340' side='right'caption='[[6e37]], [[Resolution|resolution]] 2.53&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6e37]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E37 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E37 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HQV:(2S,3R,4R,5S,6R)-3-[(2E)-but-2-enoylamino]-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-thiopyran-2-yl+[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl+dihydrogen+diphosphate+(non-preferred+name)'>HQV</scene></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein_O-GlcNAc_transferase Protein O-GlcNAc transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.255 2.4.1.255] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e37 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e37 OCA], [http://pdbe.org/6e37 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e37 RCSB], [http://www.ebi.ac.uk/pdbsum/6e37 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e37 ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[[http://www.uniprot.org/uniprot/OGT1_HUMAN OGT1_HUMAN]] Regulation of OGT activity and altered O-GlcNAcylations are implicated in diabetes and Alzheimer disease. O-GlcNAcylation of AKT1 affects insulin signaling and, possibly diabetes. Reduced O-GlcNAcylations and resulting increased phosphorylations of MAPT/TAU are observed in Alzheimer disease (AD) brain cerebrum.
+== Function ==
+[[http://www.uniprot.org/uniprot/OGT1_HUMAN OGT1_HUMAN]] Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing. Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling. Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues.<ref>PMID:12150998</ref> <ref>PMID:18288188</ref> <ref>PMID:19451179</ref> <ref>PMID:19377461</ref> <ref>PMID:20018852</ref> <ref>PMID:20018868</ref> <ref>PMID:20200153</ref> <ref>PMID:20824293</ref> <ref>PMID:21285374</ref> <ref>PMID:22121020</ref> <ref>PMID:22923583</ref> <ref>PMID:23353889</ref> <ref>PMID:23222540</ref> <ref>PMID:15361863</ref> <ref>PMID:21240259</ref>   Isoform 2: the mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line.<ref>PMID:12150998</ref> <ref>PMID:18288188</ref> <ref>PMID:19451179</ref> <ref>PMID:19377461</ref> <ref>PMID:20018852</ref> <ref>PMID:20018868</ref> <ref>PMID:20200153</ref> <ref>PMID:20824293</ref> <ref>PMID:21285374</ref> <ref>PMID:22121020</ref> <ref>PMID:22923583</ref> <ref>PMID:23353889</ref> <ref>PMID:23222540</ref> <ref>PMID:15361863</ref> <ref>PMID:21240259</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+O-GlcNAc transferase (OGT) glycosylates numerous proteins and is implicated in many diseases. To date, most OGT inhibitors lack either sufficient potency or characterized specificity in cells. We report the first targeted covalent inhibitor that predominantly reacts with OGT but does not affect other functionally similar enzymes. This study provides a new strategy to interrogate cellular OGT functions and to investigate other glycosyltransferases.
-Authors:
+Targeted covalent inhibition of O-GlcNAc transferase in cells.,Worth M, Hu CW, Li H, Fan D, Estevez A, Zhu D, Wang A, Jiang J Chem Commun (Camb). 2019 Oct 31;55(88):13291-13294. doi: 10.1039/c9cc04560k. PMID:31626249<ref>PMID:31626249</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 6e37" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Protein O-GlcNAc transferase]]
+[[Category: Jiang, J]]
+[[Category: Li, H]]
+[[Category: Inhibitor]]
+[[Category: O-glcnac transferase]]
+[[Category: Transferase-inhibitor complex]]