2img

<StructureSection load='2img' size='340' side='right' caption='[[2img]], [[Resolution|resolution]] 1.93&Aring;' scene=''>

<table><tr><td colspan='2'>[[2img]] is a 1 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=2IMG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2IMG FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLT:D-MALATE'>MLT</scene></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=2img FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2img OCA], [http://pdbe.org/2img PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2img RCSB], [http://www.ebi.ac.uk/pdbsum/2img PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2img ProSAT], [http://www.topsan.org/Proteins/NYSGXRC/2img TOPSAN]</span></td></tr>

== Function ==

[[http://www.uniprot.org/uniprot/DUS23_HUMAN DUS23_HUMAN]] Protein phosphatase that mediates dephosphorylation of proteins phosphorylated on Tyr and Ser/Thr residues. In vitro, it can dephosphorylate p44-ERK1 (MAPK3) but not p54 SAPK-beta (MAPK10) in vitro. Able to enhance activation of JNK and p38 (MAPK14).<ref>PMID:15201283</ref> <ref>PMID:15147733</ref>

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== Publication Abstract from PubMed ==

Protein phosphorylation plays a crucial role in mitogenic signal transduction and regulation of cell growth and differentiation. Dual specificity protein phosphatase 23 (DUSP23) or VHZ mediates dephosphorylation of phospho-tyrosyl (pTyr) and phospho-seryl/threonyl (pSer/pThr) residues in specific proteins. In vitro, it can dephosphorylate p44ERK1 but not p54SAPK-beta and enhance activation of c-Jun N-terminal kinase (JNK) and p38. Human VHZ, the smallest of the catalytically active protein-tyrosine phosphatases (PTP) reported to date (150 residues), is a class I Cys-based PTP and bears the distinctive active site signature motif HCXXGXXRS(T). We present the crystal structure of VHZ determined at 1.93A resolution. The polypeptide chain adopts the typical alphabetaalpha PTP fold, giving rise to a shallow active site cleft that supports dual phosphorylated substrate specificity. Within our crystals, the Thr-135-Tyr-136 from a symmetry-related molecule bind in the active site with a malate ion, where they mimic the phosphorylated TY motif of the MAPK activation loop in an enzyme-substrate/product complex. Analyses of intermolecular interactions between the enzyme and this pseudo substrate/product along with functional analysis of Phe-66, Leu-97, and Phe-99 residues provide insights into the mechanism of substrate binding and catalysis in VHZ.

 

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== References ==

[[Category: Human]]

[[Category: Agarwal, R]]

[[Category: Burley, S K]]

[[Category: Structural genomic]]

[[Category: Swaminathan, S]]

[[Category: Vhz]]