4ay6

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[[Image:4ay6.png|left|200px]]
 
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{{STRUCTURE_4ay6| PDB=4ay6 | SCENE= }}
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==Human O-GlcNAc transferase (OGT) in complex with UDP-5SGlcNAc and substrate peptide==
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<StructureSection load='4ay6' size='340' side='right'caption='[[4ay6]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4ay6]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AY6 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12V:(2S,3R,4R,5S,6R)-3-(acetylamino)-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)'>12V</scene>, <scene name='pdbligand=DNP:3-AMINO-ALANINE'>DNP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ay6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ay6 OCA], [https://pdbe.org/4ay6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ay6 RCSB], [https://www.ebi.ac.uk/pdbsum/4ay6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ay6 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://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.
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== Function ==
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[https://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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT) using unknown mechanisms of transfer and substrate recognition. Through crystallographic snapshots and mechanism-inspired chemical probes, we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor alpha-phosphate as the catalytic base as well as an essential lysine. This mechanism seems to be a unique evolutionary solution to the spatial constraints imposed by a bulky protein acceptor substrate and explains the unexpected specificity of a recently reported metabolic OGT inhibitor.
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===Human O-GlcNAc transferase (OGT) in complex with UDP-5SGlcNAc and substrate peptide===
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O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis.,Schimpl M, Zheng X, Borodkin VS, Blair DE, Ferenbach AT, Schuttelkopf AW, Navratilova I, Aristotelous T, Albarbarawi O, Robinson DA, Macnaughtan MA, van Aalten DM Nat Chem Biol. 2012 Dec;8(12):969-74. doi: 10.1038/nchembio.1108. Epub 2012 Oct, 28. PMID:23103942<ref>PMID:23103942</ref>
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{{ABSTRACT_PUBMED_23103942}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4ay6" style="background-color:#fffaf0;"></div>
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==About this Structure==
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==See Also==
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[[4ay6]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AY6 OCA].
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*[[O-GlcNAc transferase 3D structures|O-GlcNAc transferase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein O-GlcNAc transferase]]
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[[Category: Large Structures]]
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[[Category: Aalten, D M.F Van.]]
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[[Category: Aristotelous T]]
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[[Category: Aristotelous, T.]]
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[[Category: Blair DE]]
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[[Category: Blair, D E.]]
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[[Category: Borodkin VS]]
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[[Category: Borodkin, V S.]]
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[[Category: Ferenbach AT]]
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[[Category: Ferenbach, A T.]]
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[[Category: Macnaughtan MA]]
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[[Category: Macnaughtan, M A.]]
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[[Category: Navratilova I]]
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[[Category: Navratilova, I.]]
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[[Category: Schimpl M]]
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[[Category: Schimpl, M.]]
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[[Category: Schuettelkopf AW]]
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[[Category: Schuettelkopf, A W.]]
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[[Category: Zheng X]]
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[[Category: Zheng, X.]]
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[[Category: Van Aalten DMF]]
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[[Category: Glycosyl transferase]]
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[[Category: Transferase]]
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Current revision

Human O-GlcNAc transferase (OGT) in complex with UDP-5SGlcNAc and substrate peptide

PDB ID 4ay6

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