View source for 4b04


==Crystal structure of the Catalytic Domain of Human DUSP26 (C152S)==
<StructureSection load='4b04' size='340' side='right'caption='[[4b04]], [[Resolution|resolution]] 2.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4b04]] is a 4 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=4B04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B04 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]] 2.205&#8491;</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=4b04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b04 OCA], [https://pdbe.org/4b04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b04 RCSB], [https://www.ebi.ac.uk/pdbsum/4b04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b04 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DUS26_HUMAN DUS26_HUMAN] Inactivates MAPK1 and MAPK3 which leads to dephosphorylation of heat shock factor protein 4 and a reduction in its DNA-binding activity. Inhibits MAP kinase p38 by dephosphorylating it and inhibits p38-mediated apoptosis in anaplastic thyroid cancer cells. Can also induce activation of MAP kinase p38 and c-Jun N-terminal kinase (JNK).<ref>PMID:15796912</ref> <ref>PMID:16924234</ref> <ref>PMID:17001450</ref> <ref>PMID:16581800</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Dual-specificity phosphatases (DUSPs) play an important role in regulating cellular signalling pathways governing cell growth, differentiation and apoptosis. Human DUSP26 inhibits the apoptosis of cancer cells by dephosphorylating substrates such as p38 and p53. High-resolution crystal structures of the DUSP26 catalytic domain (DUSP26-C) and its C152S mutant [DUSP26-C (C152S)] have been determined at 1.67 and 2.20 A resolution, respectively. The structure of DUSP26-C showed a novel type of domain-swapped dimer formed by extensive crossover of the C-terminal alpha7 helix. Taken together with the results of a phosphatase-activity assay, structural comparison with other DUSPs revealed that DUSP26-C adopts a catalytically inactive conformation of the protein tyrosine phosphate-binding loop which significantly deviates from that of canonical DUSP structures. In particular, a noticeable difference exists between DUSP26-C and the active forms of other DUSPs at the hinge region of a swapped C-terminal domain. Additionally, two significant gaps were identified between the catalytic core and its surrounding loops in DUSP26-C, which can be exploited as additional binding sites for allosteric enzyme regulation. The high-resolution structure of DUSP26-C may thus provide structural insights into the rational design of DUSP26-targeted anticancer drugs.

High-resolution crystal structure of the catalytic domain of human dual-specificity phosphatase 26.,Won EY, Xie Y, Takemoto C, Chen L, Liu ZJ, Wang BC, Lee D, Woo EJ, Park SG, Shirouzu M, Yokoyama S, Kim SJ, Chi SW Acta Crystallogr D Biol Crystallogr. 2013 Jun;69(Pt 6):1160-70. doi:, 10.1107/S0907444913004770. Epub 2013 May 16. PMID:23695260<ref>PMID:23695260</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4b04" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]]
*[[MAP kinase phosphatase|MAP kinase phosphatase]]
*[[TATA-binding protein 3D structures|TATA-binding protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Chi S-W]]
[[Category: Kim SJ]]
[[Category: Lee DY]]
[[Category: Park SG]]
[[Category: Won E-Y]]
[[Category: Yokoyama S]]