View source for 5gtj


==CRYSTAL STRUCTURE OF CATALYTICALLY ACTIVE FORM OF HUMAN DUSP26==
<StructureSection load='5gtj' size='340' side='right'caption='[[5gtj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5gtj]] 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=5GTJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GTJ 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&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=5gtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtj OCA], [https://pdbe.org/5gtj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gtj RCSB], [https://www.ebi.ac.uk/pdbsum/5gtj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtj 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 ==
Human dual-specificity phosphatase 26 (DUSP26) is a novel target for anticancer therapy because its dephosphorylation of the p53 tumor suppressor regulates the apoptosis of cancer cells. DUSP26 inhibition results in neuroblastoma cell cytotoxicity through p53-mediated apoptosis. Despite the previous structural studies of DUSP26 catalytic domain (residues 61-211, DUSP26-C), the high-resolution structure of its catalytically active form has not been resolved. In this study, we determined the crystal structure of a catalytically active form of DUSP26 (residues 39-211, DUSP26-N) with an additional N-terminal region at 2.0 A resolution. Unlike the C-terminal domain-swapped dimeric structure of DUSP26-C, the DUSP26-N (C152S) monomer adopts a fold-back conformation of the C-terminal alpha8-helix and has an additional alpha1-helix in the N-terminal region. Consistent with the canonically active conformation of its protein tyrosine phosphate-binding loop (PTP loop) observed in the structure, the phosphatase assay results demonstrated that DUSP26-N has significantly higher catalytic activity than DUSP26-C. Furthermore, size exclusion chromatography-multiangle laser scattering (SEC-MALS) measurements showed that DUSP26-N (C152S) exists as a monomer in solution. Notably, the crystal structure of DUSP26-N (C152S) revealed that the N-terminal region of DUSP26-N (C152S) serves a scaffolding role by positioning the surrounding alpha7-alpha8 loop for interaction with the PTP-loop through formation of an extensive hydrogen bond network, which seems to be critical in making the PTP-loop conformation competent for phosphatase activity. Our study provides the first high-resolution structure of a catalytically active form of DUSP26, which will contribute to the structure-based rational design of novel DUSP26-targeting anticancer therapeutics.

Structural Insight into the Critical Role of the N-Terminal Region in the Catalytic Activity of Dual-Specificity Phosphatase 26.,Won EY, Lee SO, Lee DH, Lee D, Bae KH, Lee SC, Kim SJ, Chi SW PLoS One. 2016 Sep 1;11(9):e0162115. doi: 10.1371/journal.pone.0162115., eCollection 2016. PMID:27583453<ref>PMID:27583453</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5gtj" style="background-color:#fffaf0;"></div>

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