2y6e

From Proteopedia

(Difference between revisions)

Revision as of 17:37, 4 August 2016

Structure of the D1D2 domain of USP4, the conserved catalytic domain

Structural highlights

2y6e is a 6 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
NonStd Res:
Activity:	Ubiquitin thiolesterase, with EC number 3.1.2.15
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBP4_HUMAN] Hydrolase that deubiquitinates target proteins such as the receptor ADORA2A, PDPK1 and TRIM21. Deubiquitination of ADORA2A increases the amount of functional receptor at the cell surface. Plays a role in the regulation of quality control in the ER.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-beta response, NF-kappaB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP-Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP-Ubl domain promotes a change of a switching loop near the active site. This 'allosteric regulation of product discharge' provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes.

The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange.,Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399. PMID:25404403^[5]

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

References

↑ Gray DA, Inazawa J, Gupta K, Wong A, Ueda R, Takahashi T. Elevated expression of Unph, a proto-oncogene at 3p21.3, in human lung tumors. Oncogene. 1995 Jun 1;10(11):2179-83. PMID:7784062
↑ Wada K, Tanji K, Kamitani T. Oncogenic protein UnpEL/Usp4 deubiquitinates Ro52 by its isopeptidase activity. Biochem Biophys Res Commun. 2006 Jan 20;339(3):731-6. PMID:16316627 doi:10.1016/j.bbrc.2005.11.076
↑ Wada K, Kamitani T. UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself. Biochem Biophys Res Commun. 2006 Mar 31;342(1):253-8. Epub 2006 Feb 6. PMID:16472766 doi:10.1016/j.bbrc.2006.01.144
↑ Milojevic T, Reiterer V, Stefan E, Korkhov VM, Dorostkar MM, Ducza E, Ogris E, Boehm S, Freissmuth M, Nanoff C. The ubiquitin-specific protease Usp4 regulates the cell surface level of the A2A receptor. Mol Pharmacol. 2006 Apr;69(4):1083-94. Epub 2005 Dec 9. PMID:16339847 doi:10.1124/mol.105.015818
↑ Clerici M, Luna-Vargas MP, Faesen AC, Sixma TK. The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange. Nat Commun. 2014 Nov 18;5:5399. doi: 10.1038/ncomms6399. PMID:25404403 doi:http://dx.doi.org/10.1038/ncomms6399

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/2y6e"

@@ Line 1: / Line 1: @@
 ==Structure of the D1D2 domain of USP4, the conserved catalytic domain==
 <StructureSection load='2y6e' size='340' side='right' caption='[[2y6e]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitin_thiolesterase Ubiquitin thiolesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.2.15 3.1.2.15] </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=2y6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y6e RCSB], [http://www.ebi.ac.uk/pdbsum/2y6e PDBsum]</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=2y6e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y6e OCA], [http://pdbe.org/2y6e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y6e RCSB], [http://www.ebi.ac.uk/pdbsum/2y6e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y6e ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2y6e" style="background-color:#fffaf0;"></div>
 ==See Also==

2y6e

From Proteopedia

Revision as of 17:37, 4 August 2016

Structure of the D1D2 domain of USP4, the conserved catalytic domain

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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