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5xjv

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Two intermediate states of conformation switch in dual specificity phosphatase 13a

Structural highlights

5xjv is a 2 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 1.69Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DS13A_HUMAN Probable protein tyrosine phosphatase. Has a phosphatase activity-independent regulatory role in MAP3K5/ASK1-mediated apoptosis, preventing MAP3K5/ASK1 inhibition by AKT1. Shows no phosphatase activity on MAPK1/ERK2, MAPK8/JNK, MAPK14/p38 and MAP3K5/ASK1.^[1]

Publication Abstract from PubMed

Dual specificity phosphatases (DUSPs) include MAP kinase phosphatases and atypical dual specificity phosphatases and mediate cell growth and differentiation, brain function, and immune responses. They serve as targets for drug development against cancers, diabetes and depression. Several DUSPs have non-canonical conformation of the central beta-sheet and active site loops, suggesting that they may have conformational switch that is related to the regulation of enzyme activity. Here, we determined the crystal structure of DUSP13a, and identified two different structures that represent intermediates of the postulated conformational switch. Amino acid sequence of DUSP13a is not significantly homologous to DUSPs with conformational switch, indicating that the conformational switch is not sequence-dependent, but rather determined by ligand interaction. The sequence-independency suggests that other DUSPs with canonical conformation may have the conformational switch during specific cellular regulation. The conformational switch leads to significant changes in the protein surface, including a hydrophobic surface and pockets, which can be exploited for development of allosteric modulators of drug target DUSPs.

Two intermediate states of the conformational switch in dual specificity phosphatase 13a.,Wei CH, Min HG, Kim M, Kim GH, Chun HJ, Ryu SE Pharmacol Res. 2018 Feb;128:211-219. doi: 10.1016/j.phrs.2017.10.006. Epub 2017, Oct 27. PMID:29106959^[2]

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

References

↑ Park JE, Park BC, Kim HA, Song M, Park SG, Lee DH, Kim HJ, Choi HK, Kim JT, Cho S. Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A. Cell Mol Life Sci. 2010 Aug;67(15):2619-29. doi: 10.1007/s00018-010-0353-3. Epub , 2010 Apr 1. PMID:20358250 doi:http://dx.doi.org/10.1007/s00018-010-0353-3
↑ Wei CH, Min HG, Kim M, Kim GH, Chun HJ, Ryu SE. Two intermediate states of the conformational switch in dual specificity phosphatase 13a. Pharmacol Res. 2018 Feb;128:211-219. doi: 10.1016/j.phrs.2017.10.006. Epub 2017, Oct 27. PMID:29106959 doi:http://dx.doi.org/10.1016/j.phrs.2017.10.006

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/5xjv"

@@ Line 1: / Line 1: @@
 ==Two intermediate states of conformation switch in dual specificity phosphatase 13a==
-<StructureSection load='5xjv' size='340' side='right' caption='[[5xjv]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
+<StructureSection load='5xjv' size='340' side='right'caption='[[5xjv]], [[Resolution|resolution]] 1.69&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5xjv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XJV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XJV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5xjv]] is a 2 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=5XJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XJV 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]] 1.69&#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=5xjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjv OCA], [http://pdbe.org/5xjv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xjv RCSB], [http://www.ebi.ac.uk/pdbsum/5xjv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjv 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=5xjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xjv OCA], [https://pdbe.org/5xjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xjv RCSB], [https://www.ebi.ac.uk/pdbsum/5xjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xjv ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DS13A_HUMAN DS13A_HUMAN]] Probable protein tyrosine phosphatase. Has a phosphatase activity-independent regulatory role in MAP3K5/ASK1-mediated apoptosis, preventing MAP3K5/ASK1 inhibition by AKT1. Shows no phosphatase activity on MAPK1/ERK2, MAPK8/JNK, MAPK14/p38 and MAP3K5/ASK1.<ref>PMID:20358250</ref>
+[https://www.uniprot.org/uniprot/DS13A_HUMAN DS13A_HUMAN] Probable protein tyrosine phosphatase. Has a phosphatase activity-independent regulatory role in MAP3K5/ASK1-mediated apoptosis, preventing MAP3K5/ASK1 inhibition by AKT1. Shows no phosphatase activity on MAPK1/ERK2, MAPK8/JNK, MAPK14/p38 and MAP3K5/ASK1.<ref>PMID:20358250</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5xjv" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Chun, H J]]
+[[Category: Homo sapiens]]
-[[Category: Min, H G]]
+[[Category: Large Structures]]
-[[Category: Ryu, S E]]
+[[Category: Chun HJ]]
-[[Category: Wei, C H]]
+[[Category: Min HG]]
-[[Category: Catalytic domain]]
+[[Category: Ryu SE]]
-[[Category: Conformation switch]]
+[[Category: Wei CH]]
-[[Category: Dusp13a]]
-[[Category: Hydrolase]]
-[[Category: Ptp]]

5xjv

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Current revision

Two intermediate states of conformation switch in dual specificity phosphatase 13a

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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