View source for 4gyw


==Crystal structure of human O-GlcNAc Transferase in complex with UDP and a glycopeptide==
<StructureSection load='4gyw' size='340' side='right'caption='[[4gyw]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4gyw]] is a 4 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=4GYW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GYW 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=4gyw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gyw OCA], [https://pdbe.org/4gyw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gyw RCSB], [https://www.ebi.ac.uk/pdbsum/4gyw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gyw ProSAT]</span></td></tr>
</table>
== Disease ==
[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.
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Visualization of the reaction coordinate undertaken by glycosyltransferases has remained elusive but is critical for understanding this important class of enzyme. Using substrates and substrate mimics, we describe structural snapshots of all species along the kinetic pathway for human O-linked beta-N-acetylglucosamine transferase (O-GlcNAc transferase), an intracellular enzyme that catalyzes installation of a dynamic post-translational modification. The structures reveal key features of the mechanism and show that substrate participation is important during catalysis.

Structural snapshots of the reaction coordinate for O-GlcNAc transferase.,Lazarus MB, Jiang J, Gloster TM, Zandberg WF, Whitworth GE, Vocadlo DJ, Walker S Nat Chem Biol. 2012 Dec;8(12):966-8. doi: 10.1038/nchembio.1109. Epub 2012 Oct, 28. PMID:23103939<ref>PMID:23103939</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4gyw" style="background-color:#fffaf0;"></div>

==See Also==
*[[O-GlcNAc transferase 3D structures|O-GlcNAc transferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gloster TM]]
[[Category: Jiang J]]
[[Category: Lazarus MB]]
[[Category: Vocadlo DJ]]
[[Category: Walker S]]
[[Category: Zandberg WF]]