5xve

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of human USP2 C276S mutant in complex with ubiquitin

Structural highlights

5xve is a 2 chain structure with sequence from Bos taurus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.24Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

UBP2_HUMAN Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities. Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity. Has no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated degradation of MDM4. Plays a role in the G1/S cell-cycle progression in normal and cancer cells. Plays a role in the regulation of myogenic differentiation of embryonic muscle cells.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases that can rescue protein targets from proteasomal degradation by reversing their ubiquitination. In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP2 thus plays a critical role in tumor cells' survival and therefore represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found to be a potent inhibitor of USP2. Enzyme-kinetic and X-ray crystallographic data suggest that 6-thioguanine displays a noncompetitive and slow-binding inhibitory mechanism against USP2. Our study provides a clear rationale for the clinical evaluation of 6-thioguanine for USP2-upregulated cancers.

6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2.,Chuang SJ, Cheng SC, Tang HC, Sun CY, Chou CY Sci Rep. 2018 Feb 15;8(1):3102. doi: 10.1038/s41598-018-21476-w. PMID:29449607^[4]

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

References

↑ Stevenson LF, Sparks A, Allende-Vega N, Xirodimas DP, Lane DP, Saville MK. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. EMBO J. 2007 Feb 21;26(4):976-86. Epub 2007 Feb 8. PMID:17290220 doi:10.1038/sj.emboj.7601567
↑ Shan J, Zhao W, Gu W. Suppression of cancer cell growth by promoting cyclin D1 degradation. Mol Cell. 2009 Nov 13;36(3):469-76. doi: 10.1016/j.molcel.2009.10.018. PMID:19917254 doi:10.1016/j.molcel.2009.10.018
↑ Allende-Vega N, Sparks A, Lane DP, Saville MK. MdmX is a substrate for the deubiquitinating enzyme USP2a. Oncogene. 2010 Jan 21;29(3):432-41. doi: 10.1038/onc.2009.330. Epub 2009 Oct 19. PMID:19838211 doi:10.1038/onc.2009.330
↑ Chuang SJ, Cheng SC, Tang HC, Sun CY, Chou CY. 6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2. Sci Rep. 2018 Feb 15;8(1):3102. doi: 10.1038/s41598-018-21476-w. PMID:29449607 doi:http://dx.doi.org/10.1038/s41598-018-21476-w

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/5xve"

Categories: Bos taurus | Homo sapiens | Large Structures | Chou CY | Tang HC

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5xve is ON HOLD  until Paper Publication
+==Crystal structure of human USP2 C276S mutant in complex with ubiquitin==
+<StructureSection load='5xve' size='340' side='right'caption='[[5xve]], [[Resolution|resolution]] 1.24&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5xve]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XVE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XVE 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]] 1.24&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5xve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xve OCA], [https://pdbe.org/5xve PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xve RCSB], [https://www.ebi.ac.uk/pdbsum/5xve PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xve ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/UBP2_HUMAN UBP2_HUMAN] Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1. Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities. Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity. Has no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated degradation of MDM4. Plays a role in the G1/S cell-cycle progression in normal and cancer cells. Plays a role in the regulation of myogenic differentiation of embryonic muscle cells.<ref>PMID:17290220</ref> <ref>PMID:19917254</ref> <ref>PMID:19838211</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ubiquitin-specific protease 2 (USP2) belongs to the family of deubiquitinases that can rescue protein targets from proteasomal degradation by reversing their ubiquitination. In various cancers, including prostate cancer and ovarian carcinoma, upregulation of USP2 leads to an increase in the levels of deubiquitinated substrates such as fatty acid synthase, MDM2, cyclin D1 and Aurora-A. USP2 thus plays a critical role in tumor cells' survival and therefore represents a therapeutic target. Here a leukemia drug, 6-thioguanine, was found to be a potent inhibitor of USP2. Enzyme-kinetic and X-ray crystallographic data suggest that 6-thioguanine displays a noncompetitive and slow-binding inhibitory mechanism against USP2. Our study provides a clear rationale for the clinical evaluation of 6-thioguanine for USP2-upregulated cancers.
-Authors: Chou, C.Y., Tang, H.C.
+-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2.,Chuang SJ, Cheng SC, Tang HC, Sun CY, Chou CY Sci Rep. 2018 Feb 15;8(1):3102. doi: 10.1038/s41598-018-21476-w. PMID:29449607<ref>PMID:29449607</ref>
-Description: Crystal structure of human USP2 C276S mutant in complex with ubiquitin
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Chou, C.Y]]
+<div class="pdbe-citations 5xve" style="background-color:#fffaf0;"></div>
-[[Category: Tang, H.C]]
+==See Also==
+*[[Thioesterase 3D structures|Thioesterase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Bos taurus]]
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chou CY]]
+[[Category: Tang HC]]

5xve

From Proteopedia

Current revision

Crystal structure of human USP2 C276S mutant in complex with ubiquitin

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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