5vif

From Proteopedia

(Difference between revisions)

Revision as of 13:49, 4 October 2023

Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase

Structural highlights

5vif is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.25Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CSK21_HUMAN Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

O-linked beta-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. However, little is known about the mechanism with which OGT recognizes various protein substrates. Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition. Data from mass spectrometry, X-ray crystallization, and biochemical and radiolabeled kinetic assays support the application of GEPs to rapidly report the impacts of OGT mutations on protein substrate or sugar binding and to discover OGT residues crucial for protein recognition. Interestingly, we found that the same residues on the inner surface of the N-terminal domain contribute to OGT interactions with different protein substrates. By tuning reaction conditions, a GEP enables crosslinking of OGT with acceptor substrates in situ, affording a unique method to discover genuine substrates that weakly or transiently interact with OGT. Hence, GEPs provide new strategies to dissect OGT-substrate binding and recognition.

Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase.,Hu CW, Worth M, Fan D, Li B, Li H, Lu L, Zhong X, Lin Z, Wei L, Ge Y, Li L, Jiang J Nat Chem Biol. 2017 Oct 23. doi: 10.1038/nchembio.2494. PMID:29058723^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H. A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. Mol Cell. 2001 Feb;7(2):283-92. PMID:11239457
↑ Sayed M, Pelech S, Wong C, Marotta A, Salh B. Protein kinase CK2 is involved in G2 arrest and apoptosis following spindle damage in epithelial cells. Oncogene. 2001 Oct 25;20(48):6994-7005. PMID:11704824 doi:10.1038/sj.onc.1204894
↑ Shin S, Lee Y, Kim W, Ko H, Choi H, Kim K. Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8. EMBO J. 2005 Oct 19;24(20):3532-42. Epub 2005 Sep 29. PMID:16193064 doi:10.1038/sj.emboj.7600827
↑ St-Denis NA, Derksen DR, Litchfield DW. Evidence for regulation of mitotic progression through temporal phosphorylation and dephosphorylation of CK2alpha. Mol Cell Biol. 2009 Apr;29(8):2068-81. doi: 10.1128/MCB.01563-08. Epub 2009 Feb, 2. PMID:19188443 doi:10.1128/MCB.01563-08
↑ Hu CW, Worth M, Fan D, Li B, Li H, Lu L, Zhong X, Lin Z, Wei L, Ge Y, Li L, Jiang J. Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase. Nat Chem Biol. 2017 Oct 23. doi: 10.1038/nchembio.2494. PMID:29058723 doi:http://dx.doi.org/10.1038/nchembio.2494

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5vif"

@@ Line 1: / Line 1: @@
 ==Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase==
-<StructureSection load='5vif' size='340' side='right' caption='[[5vif]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+<StructureSection load='5vif' size='340' side='right'caption='[[5vif]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5vif]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VIF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VIF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5vif]] 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=5VIF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VIF FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9C1:2-{[(2E)-4-chlorobut-2-enoyl]amino}-2-deoxy-beta-D-glucopyranose'>9C1</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5vie|5vie]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9C1:2-{[(2E)-4-chlorobut-2-enoyl]amino}-2-deoxy-beta-D-glucopyranose'>9C1</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">OGT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5vif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vif OCA], [https://pdbe.org/5vif PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vif RCSB], [https://www.ebi.ac.uk/pdbsum/5vif PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vif ProSAT]</span></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=5vif FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vif OCA], [http://pdbe.org/5vif PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vif RCSB], [http://www.ebi.ac.uk/pdbsum/5vif PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vif 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>
+[https://www.uniprot.org/uniprot/CSK21_HUMAN CSK21_HUMAN] Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV.<ref>PMID:11239457</ref> <ref>PMID:11704824</ref> <ref>PMID:16193064</ref> <ref>PMID:19188443</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 19: @@
 </div>
 <div class="pdbe-citations 5vif" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[O-GlcNAc transferase 3D structures|O-GlcNAc transferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Protein O-GlcNAc transferase]]
+[[Category: Large Structures]]
-[[Category: Fan, D]]
+[[Category: Fan D]]
-[[Category: Hu, C W]]
+[[Category: Hu C-W]]
-[[Category: Jiang, J]]
+[[Category: Jiang J]]
-[[Category: Li, B]]
+[[Category: Li B]]
-[[Category: Li, H]]
+[[Category: Li H]]
-[[Category: Worth, M]]
+[[Category: Worth M]]
-[[Category: Ckii]]
-[[Category: Glycosylation electrophilic probe]]
-[[Category: O-glcnac transferase]]
-[[Category: Transferase]]

5vif

From Proteopedia

Revision as of 13:49, 4 October 2023

Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox