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| | ==Human PP2Calpha (PPM1A) complexed with cyclic peptide c(MpSIpYVA)== | | ==Human PP2Calpha (PPM1A) complexed with cyclic peptide c(MpSIpYVA)== |
| - | <StructureSection load='6b67' size='340' side='right' caption='[[6b67]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='6b67' size='340' side='right'caption='[[6b67]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6b67]] is a 6 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=6B67 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B67 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b67]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B67 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 2.2Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=48V:{[(2R)-2,3-DIAMINO-3-OXOPROPYL]SULFANYL}ACETIC+ACID'>48V</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=48V:{[(2R)-2,3-DIAMINO-3-OXOPROPYL]SULFANYL}ACETIC+ACID'>48V</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPM1A, PPPM1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6b67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b67 OCA], [https://pdbe.org/6b67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b67 RCSB], [https://www.ebi.ac.uk/pdbsum/6b67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b67 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span></td></tr>
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| - | <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=6b67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b67 OCA], [http://pdbe.org/6b67 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b67 RCSB], [http://www.ebi.ac.uk/pdbsum/6b67 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b67 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6b67" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6b67" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Dyda, F]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Kosek, D]] | + | [[Category: Dyda F]] |
| - | [[Category: Hydrolase]] | + | [[Category: Kosek D]] |
| - | [[Category: Phosphatase]]
| + | |
| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
Metal-dependent protein phosphatases (PPM) are evolutionarily unrelated to other serine/threonine protein phosphatases and are characterized by their requirement for supplementation with millimolar concentrations of Mg(2+) or Mn(2+) ions for activity in vitro The crystal structure of human PPM1A (also known as PP2Calpha), the first PPM structure determined, displays two tightly bound Mn(2+) ions in the active site and a small subdomain, termed the Flap, located adjacent to the active site. Some recent crystal structures of bacterial or plant PPM phosphatases have disclosed two tightly bound metal ions and an additional, third metal ion in the active site. Here, the crystal structure of the catalytic domain of human PPM1A, PPM1Acat, complexed with a cyclic phosphopeptide, c(MpSIpYVA), a cyclized variant of the activation loop of p38 MAPK (a physiological substrate of PPM1A), revealed three metal ions in the active site. The PPM1Acat D146Ec(MpSIpYVA) complex confirmed the presence of the anticipated third metal ion in the active site of metazoan PPM phosphatases. Biophysical and computational methods suggested that complex formation results in a slightly more compact solution conformation through reduced conformational flexibility of the Flap subdomain. We also observed that the position of the substrate in the active site allows solvent access to the labile third metal-binding site. Enzyme kinetics of PPM1Acat toward a phosphopeptide substrate supported a random-order, bi-substrate mechanism, with substantial interaction between the bound substrate and the labile metal ion. This work illuminates the structural and thermodynamic basis of an innate mechanism regulating the activity of PPM phosphatases.
A trapped human PPM1A-phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity.,Debnath S, Kosek D, Tagad HD, Durell SR, Appella DH, Acevedo R, Grishaev A, Dyda F, Appella E, Mazur SJ J Biol Chem. 2018 Mar 30. pii: RA117.001213. doi: 10.1074/jbc.RA117.001213. PMID:29602904[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lin X, Duan X, Liang YY, Su Y, Wrighton KH, Long J, Hu M, Davis CM, Wang J, Brunicardi FC, Shi Y, Chen YG, Meng A, Feng XH. PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 2006 Jun 2;125(5):915-28. PMID:16751101 doi:10.1016/j.cell.2006.03.044
- ↑ Debnath S, Kosek D, Tagad HD, Durell SR, Appella DH, Acevedo R, Grishaev A, Dyda F, Appella E, Mazur SJ. A trapped human PPM1A-phosphopeptide complex reveals structural features critical for regulation of PPM protein phosphatase activity. J Biol Chem. 2018 Mar 30. pii: RA117.001213. doi: 10.1074/jbc.RA117.001213. PMID:29602904 doi:http://dx.doi.org/10.1074/jbc.RA117.001213
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