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New page: left|200px<br /> <applet load="1a6q" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a6q, resolution 2.0Å" /> '''CRYSTAL STRUCTURE OF...
 
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[[Image:1a6q.gif|left|200px]]<br />
<applet load="1a6q" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1a6q, resolution 2.0&Aring;" />
'''CRYSTAL STRUCTURE OF THE PROTEIN SERINE/THREONINE PHOSPHATASE 2C AT 2 A RESOLUTION'''<br />


==Overview==
==CRYSTAL STRUCTURE OF THE PROTEIN SERINE/THREONINE PHOSPHATASE 2C AT 2 A RESOLUTION==
Protein phosphatase 2C (PP2C) is a Mn2+- or Mg2+-dependent protein Ser/Thr, phosphatase that is essential for regulating cellular stress responses in, eukaryotes. The crystal structure of human PP2C reveals a novel protein, fold with a catalytic domain composed of a central beta-sandwich that, binds two manganese ions, which is surrounded by alpha-helices. Mn2+-bound, water molecules at the binuclear metal centre coordinate the phosphate, group of the substrate and provide a nucleophile and general acid in the, dephosphorylation reaction. Our model presents a framework for, understanding not only the classical Mn2+/Mg2+-dependent protein, phosphatases but also the sequence-related domains of mitochondrial, pyruvate dehydrogenase phosphatase, the Bacillus subtilus phosphatase, SpoIIE and a ... [[http://ispc.weizmann.ac.il/pmbin/getpm?9003755 (full description)]]
<StructureSection load='1a6q' size='340' side='right'caption='[[1a6q]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1a6q]] is a 1 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=1A6Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A6Q FirstGlance]. <br>
</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <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=1a6q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a6q OCA], [https://pdbe.org/1a6q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a6q RCSB], [https://www.ebi.ac.uk/pdbsum/1a6q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a6q ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PPM1A_HUMAN PPM1A_HUMAN] Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling.<ref>PMID:16751101</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/a6/1a6q_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1a6q ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein phosphatase 2C (PP2C) is a Mn2+- or Mg2+-dependent protein Ser/Thr phosphatase that is essential for regulating cellular stress responses in eukaryotes. The crystal structure of human PP2C reveals a novel protein fold with a catalytic domain composed of a central beta-sandwich that binds two manganese ions, which is surrounded by alpha-helices. Mn2+-bound water molecules at the binuclear metal centre coordinate the phosphate group of the substrate and provide a nucleophile and general acid in the dephosphorylation reaction. Our model presents a framework for understanding not only the classical Mn2+/Mg2+-dependent protein phosphatases but also the sequence-related domains of mitochondrial pyruvate dehydrogenase phosphatase, the Bacillus subtilus phosphatase SpoIIE and a 300-residue domain within yeast adenyl cyclase. The protein architecture and deduced catalytic mechanism are strikingly similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence similarity, suggestive of convergent evolution of protein Ser/Thr phosphatases.


==About this Structure==
Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution.,Das AK, Helps NR, Cohen PT, Barford D EMBO J. 1996 Dec 16;15(24):6798-809. PMID:9003755<ref>PMID:9003755</ref>
1A6Q is a [[http://en.wikipedia.org/wiki/Single_protein Single protein]] structure of sequence from [[http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]] with MN and PO4 as [[http://en.wikipedia.org/wiki/ligands ligands]]. Active as [[http://en.wikipedia.org/wiki/ ]], with EC number [[http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16]]. Full crystallographic information is available from [[http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A6Q OCA]].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Crystal structure of the protein serine/threonine phosphatase 2C at 2.0 A resolution., Das AK, Helps NR, Cohen PT, Barford D, EMBO J. 1996 Dec 16;15(24):6798-809. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9003755 9003755]
</div>
<div class="pdbe-citations 1a6q" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Barford, D.]]
[[Category: Barford D]]
[[Category: Cohen, P.T.W.]]
[[Category: Cohen PTW]]
[[Category: Das, A.K.]]
[[Category: Das AK]]
[[Category: Helps, N.R.]]
[[Category: Helps NR]]
[[Category: MN]]
[[Category: PO4]]
[[Category: catalytic mechanism]]
[[Category: hydrolase]]
[[Category: metalloenzyme]]
[[Category: protein phosphatase 2c]]
[[Category: signal transductuin]]
[[Category: x-ray crystallography]]
 
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