5gtj

From Proteopedia

(Difference between revisions)

Current revision

CRYSTAL STRUCTURE OF CATALYTICALLY ACTIVE FORM OF HUMAN DUSP26

Structural highlights

5gtj is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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).^[1] ^[2] ^[3] ^[4]

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^[5]

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

References

↑ Vasudevan SA, Skoko J, Wang K, Burlingame SM, Patel PN, Lazo JS, Nuchtern JG, Yang J. MKP-8, a novel MAPK phosphatase that inhibits p38 kinase. Biochem Biophys Res Commun. 2005 May 6;330(2):511-8. PMID:15796912 doi:10.1016/j.bbrc.2005.03.028
↑ Yu W, Imoto I, Inoue J, Onda M, Emi M, Inazawa J. A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity. Oncogene. 2007 Feb 22;26(8):1178-87. Epub 2006 Aug 21. PMID:16924234 doi:10.1038/sj.onc.1209899
↑ Takagaki K, Shima H, Tanuma N, Nomura M, Satoh T, Watanabe M, Kikuchi K. Characterization of a novel low-molecular-mass dual specificity phosphatase-4 (LDP-4) expressed in brain. Mol Cell Biochem. 2007 Feb;296(1-2):177-84. Epub 2006 Sep 26. PMID:17001450 doi:10.1007/s11010-006-9313-5
↑ Hu Y, Mivechi NF. Association and regulation of heat shock transcription factor 4b with both extracellular signal-regulated kinase mitogen-activated protein kinase and dual-specificity tyrosine phosphatase DUSP26. Mol Cell Biol. 2006 Apr;26(8):3282-94. PMID:16581800 doi:26/8/3282
↑ Won EY, Lee SO, Lee DH, Lee D, Bae KH, Lee SC, Kim SJ, Chi SW. Structural Insight into the Critical Role of the N-Terminal Region in the Catalytic Activity of Dual-Specificity Phosphatase 26. PLoS One. 2016 Sep 1;11(9):e0162115. doi: 10.1371/journal.pone.0162115., eCollection 2016. PMID:27583453 doi:http://dx.doi.org/10.1371/journal.pone.0162115

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/5gtj"

Categories: Homo sapiens | Large Structures | Chi S-W | Kim SJ | Won E-Y

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF CATALYTICALLY ACTIVE FORM OF HUMAN DUSP26==
-<StructureSection load='5gtj' size='340' side='right' caption='[[5gtj]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<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. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GTJ FirstGlance]. <br>
+<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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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]] 2&#8491;</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=5gtj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gtj OCA], [http://pdbe.org/5gtj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gtj RCSB], [http://www.ebi.ac.uk/pdbsum/5gtj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gtj ProSAT]</span></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 ==
-[[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;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <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: Chi, S W]]
+[[Category: Homo sapiens]]
-[[Category: Kim, S J]]
+[[Category: Large Structures]]
-[[Category: Won, E Y]]
+[[Category: Chi S-W]]
-[[Category: Active form]]
+[[Category: Kim SJ]]
-[[Category: Hydrolase]]
+[[Category: Won E-Y]]

5gtj

From Proteopedia

Current revision

CRYSTAL STRUCTURE OF CATALYTICALLY ACTIVE FORM OF HUMAN DUSP26

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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