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| | ==Atomic structure of DUSP26== | | ==Atomic structure of DUSP26== |
| - | <StructureSection load='4hrf' size='340' side='right' caption='[[4hrf]], [[Resolution|resolution]] 1.68Å' scene=''> | + | <StructureSection load='4hrf' size='340' side='right'caption='[[4hrf]], [[Resolution|resolution]] 1.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hrf]] is a 4 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=4HRF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HRF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hrf]] 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=4HRF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HRF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3cm3|3cm3]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.68Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DUSP24, DUSP26, LDP4, MKP8, NATA1, SKRP3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4hrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hrf OCA], [https://pdbe.org/4hrf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hrf RCSB], [https://www.ebi.ac.uk/pdbsum/4hrf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hrf ProSAT]</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=4hrf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hrf OCA], [http://pdbe.org/4hrf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4hrf RCSB], [http://www.ebi.ac.uk/pdbsum/4hrf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4hrf ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;">
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| - | == Publication Abstract from PubMed ==
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| - | Regulation of p53 phosphorylation is critical to control its stability and biological activity. Dual-specificity phosphatase 26 (DUSP26) is a brain phosphatase highly overexpressed in neuroblastoma, which has been implicated in dephosphorylating phospho-Ser20 and phospho-Ser37 in the p53 transactivation domain. In this paper, we report the 1.68 A crystal structure of a catalytically inactive mutant (Cys152Ser) of DUSP26 lacking the first 60 N-terminal residues (DeltaN60-C/S-DUSP26). This structure reveals the architecture of a dual-specificity phosphatase domain related in structure to Vaccinia virus VH1. DUSP26 adopts a closed conformation of the protein tyrosine phosphatase (PTP)-binding loop, which results in an unusually shallow active site pocket and buried catalytic cysteine. A water molecule trapped inside the PTP-binding loop makes close contacts both with main chain and with side chain atoms. The hydrodynamic radius (R(H)) of DeltaN60-C/S-DUSP26 measured from velocity sedimentation analysis (R(H) approximately 22.7 A) and gel filtration chromatography (R(H) approximately 21.0 A) is consistent with an approximately 18 kDa globular monomeric protein. Instead in crystal, DeltaN60-C/S-DUSP26 is more elongated (R(H) approximately 37.9 A), likely because of the extended conformation of C-terminal helix alpha9, which swings away from the phosphatase core to generate a highly basic surface. As in the case of phosphatase MKP-4, we propose that a substrate-induced conformational change, possibly involving rearrangement of helix alpha9 with respect to the phosphatase core, allows DUSP26 to adopt a catalytically active conformation. The structural characterization of DUSP26 presented in this paper provides the first atomic insight into this disease-associated phosphatase.
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| - | Atomic Structure of Dual-Specificity Phosphatase 26, a Novel p53 Phosphatase.,Lokareddy RK, Bhardwaj A, Cingolani G Biochemistry. 2013 Jan 18. PMID:23298255<ref>PMID:23298255</ref>
| + | ==See Also== |
| - | | + | *[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | *[[MAP kinase phosphatase|MAP kinase phosphatase]] |
| - | </div>
| + | |
| - | <div class="pdbe-citations 4hrf" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Bhardwaj, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Cingolani, G]] | + | [[Category: Bhardwaj A]] |
| - | [[Category: Lokareddy, R K]] | + | [[Category: Cingolani G]] |
| - | [[Category: Dual specificity phosphatase]] | + | [[Category: Lokareddy RK]] |
| - | [[Category: Hydrolase]]
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| - | [[Category: Nucleus]]
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| - | [[Category: P53]]
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| - | [[Category: Protein tyrosine phosphatase]]
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