4n39

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:31, 1 March 2024) (edit) (undo)
 
(3 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_4n39| PDB=4n39 | SCENE= }}
 
-
===Crystal structure of human O-GlcNAc transferase bound to a peptide from HCF-1 pro-repeat 2 (11-26)===
 
-
{{ABSTRACT_PUBMED_24311690}}
 
-
==Disease==
+
==Crystal structure of human O-GlcNAc transferase bound to a peptide from HCF-1 pro-repeat 2 (11-26)==
-
[[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. [[http://www.uniprot.org/uniprot/HCFC1_HUMAN HCFC1_HUMAN]] X-linked nonsyndromic intellectual deficit. Mental retardation, X-linked 3 (MRX3) [MIM:[http://omim.org/entry/309541 309541]]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:23000143</ref>
+
<StructureSection load='4n39' size='340' side='right'caption='[[4n39]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4n39]] is a 2 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=4N39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N39 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]] 1.76&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=4n39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n39 OCA], [https://pdbe.org/4n39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n39 RCSB], [https://www.ebi.ac.uk/pdbsum/4n39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n39 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>
-
==Function==
+
==See Also==
-
[[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> [[http://www.uniprot.org/uniprot/HCFC1_HUMAN HCFC1_HUMAN]] Involved in control of the cell cycle. Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300. Coactivator for EGR2 and GABP2. Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes.<ref>PMID:10920196</ref> <ref>PMID:9990006</ref> <ref>PMID:10675337</ref> <ref>PMID:10629049</ref> <ref>PMID:10779346</ref> <ref>PMID:12244100</ref> <ref>PMID:14532282</ref> <ref>PMID:12670868</ref> <ref>PMID:15190068</ref> <ref>PMID:16624878</ref> <ref>PMID:17578910</ref> <ref>PMID:20018852</ref> <ref>PMID:20200153</ref>
+
*[[O-GlcNAc transferase 3D structures|O-GlcNAc transferase 3D structures]]
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
[[4n39]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N39 OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
[[Category: Homo sapiens]]
-
<ref group="xtra">PMID:024311690</ref><references group="xtra"/><references/>
+
[[Category: Large Structures]]
-
[[Category: Protein O-GlcNAc transferase]]
+
[[Category: Herr W]]
-
[[Category: Herr, W.]]
+
[[Category: Lazarus MB]]
-
[[Category: Lazarus, M B.]]
+
[[Category: Walker S]]
-
[[Category: Walker, S.]]
+
-
[[Category: Glycosyltransferase]]
+
-
[[Category: O-glcnac transferase]]
+
-
[[Category: Proteolysis substrate]]
+
-
[[Category: Tpr binding]]
+
-
[[Category: Tpr domain]]
+
-
[[Category: Transferase-substrate complex]]
+

Current revision

Crystal structure of human O-GlcNAc transferase bound to a peptide from HCF-1 pro-repeat 2 (11-26)

PDB ID 4n39

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Personal tools