6q4m: Difference between revisions
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==Crystal structure of the O-GlcNAc transferase Asn648Tyr mutation== | |||
<StructureSection load='6q4m' size='340' side='right'caption='[[6q4m]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6q4m]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Q4M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6Q4M FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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'>12V</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |||
[[Category: | <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=6q4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6q4m OCA], [http://pdbe.org/6q4m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6q4m RCSB], [http://www.ebi.ac.uk/pdbsum/6q4m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6q4m 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> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Protein O-GlcNAc transferase]] | |||
[[Category: Aalten, D M.F van]] | |||
[[Category: Gundogdu, M]] | |||
[[Category: Acceptor peptide]] | |||
[[Category: Disease]] | |||
[[Category: Glycosyltransferase]] | |||
[[Category: Mutation]] | |||
[[Category: Transferase]] | |||