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5ngz

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Revision as of 12:04, 26 August 2020

Ube2T in complex with fragment EM04

Structural highlights

5ngz is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	UBE2T, HSPC150, PIG50 (HUMAN)
Activity:	E2 ubiquitin-conjugating enzyme, with EC number 2.3.2.23
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBE2T_HUMAN] Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair: acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCL and FANCI. May contribute to ubiquitination and degradation of BRCA1. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Ube2T is the E2 ubiquitin-conjugating enzyme of the Fanconi anemia DNA repair pathway and it is overexpressed in several cancers, representing an attractive target for the development of inhibitors. Despite the extensive efforts in targeting the ubiquitin system, very few E2 binders have currently been discovered. Herein we report the identification of a new allosteric pocket on Ube2T through a fragment screening using biophysical methods. Several fragments binding to this site inhibit ubiquitin conjugation in vitro.

Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening.,Morreale FE, Bortoluzzi A, Chaugule VK, Arkinson C, Walden H, Ciulli A J Med Chem. 2017 May 2. doi: 10.1021/acs.jmedchem.7b00147. PMID:28437106^[7]

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

References

↑ Machida YJ, Machida Y, Chen Y, Gurtan AM, Kupfer GM, D'Andrea AD, Dutta A. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Mol Cell. 2006 Aug;23(4):589-96. PMID:16916645 doi:http://dx.doi.org/10.1016/j.molcel.2006.06.024
↑ Alpi A, Langevin F, Mosedale G, Machida YJ, Dutta A, Patel KJ. UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Mol Cell Biol. 2007 Dec;27(24):8421-30. Epub 2007 Oct 15. PMID:17938197 doi:http://dx.doi.org/10.1128/MCB.00504-07
↑ Alpi AF, Pace PE, Babu MM, Patel KJ. Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Mol Cell. 2008 Dec 26;32(6):767-77. doi: 10.1016/j.molcel.2008.12.003. PMID:19111657 doi:http://dx.doi.org/10.1016/j.molcel.2008.12.003
↑ Ueki T, Park JH, Nishidate T, Kijima K, Hirata K, Nakamura Y, Katagiri T. Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cells. Cancer Res. 2009 Nov 15;69(22):8752-60. doi: 10.1158/0008-5472.CAN-09-1809. Epub , 2009 Nov 3. PMID:19887602 doi:http://dx.doi.org/10.1158/0008-5472.CAN-09-1809
↑ Longerich S, San Filippo J, Liu D, Sung P. FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL. J Biol Chem. 2009 Aug 28;284(35):23182-6. doi: 10.1074/jbc.C109.038075. Epub 2009, Jul 8. PMID:19589784 doi:http://dx.doi.org/10.1074/jbc.C109.038075
↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
↑ Morreale FE, Bortoluzzi A, Chaugule VK, Arkinson C, Walden H, Ciulli A. Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening. J Med Chem. 2017 May 2. doi: 10.1021/acs.jmedchem.7b00147. PMID:28437106 doi:http://dx.doi.org/10.1021/acs.jmedchem.7b00147

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Ube2T in complex with fragment EM04==
-<StructureSection load='5ngz' size='340' side='right' caption='[[5ngz]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5ngz' size='340' side='right'caption='[[5ngz]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5ngz]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NGZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NGZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5ngz]] is a 1 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=5NGZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NGZ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2BG:1-(1,3-BENZOTHIAZOL-2-YL)METHANAMINE'>2BG</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2BG:1-(1,3-BENZOTHIAZOL-2-YL)METHANAMINE'>2BG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UBE2T, HSPC150, PIG50 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/E2_ubiquitin-conjugating_enzyme E2 ubiquitin-conjugating enzyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.2.23 2.3.2.23] </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=5ngz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ngz OCA], [http://pdbe.org/5ngz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ngz RCSB], [http://www.ebi.ac.uk/pdbsum/5ngz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ngz ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5ngz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ngz OCA], [http://pdbe.org/5ngz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ngz RCSB], [http://www.ebi.ac.uk/pdbsum/5ngz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ngz ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 24: / Line 25: @@
 </StructureSection>
 [[Category: E2 ubiquitin-conjugating enzyme]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Arkinson, C]]
 [[Category: Bortoluzzi, A]]

5ngz

From Proteopedia

Revision as of 12:04, 26 August 2020

Ube2T in complex with fragment EM04

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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