2e0t

Crystal structure of catalytic domain of dual specificity phosphatase 26, MS0830 from Homo sapiens

spinqualitylabelsall models 2e0t, resolution 1.67Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2e0t is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Activity: Protein-tyrosine-phosphatase, with EC number 3.1.3.48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT, TOPSAN Function [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). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dual specificity phosphatase 3D structures

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