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| | <StructureSection load='3e7a' size='340' side='right'caption='[[3e7a]], [[Resolution|resolution]] 1.63Å' scene=''> | | <StructureSection load='3e7a' size='340' side='right'caption='[[3e7a]], [[Resolution|resolution]] 1.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3e7a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3e7a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Nodularia_spumigena Nodularia spumigena]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3E7A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3E7A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 1.63Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1ZN:(2S,3S,4E,6E,8S,9S)-3-AMINO-9-METHOXY-2,6,8-TRIMETHYL-10-PHENYLDECA-4,6-DIENOIC+ACID'>1ZN</scene>, <scene name='pdbligand=ACB:3-METHYL-BETA-D-ASPARTIC+ACID'>ACB</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene>, <scene name='pdbligand=MDH:N-METHYLDEHYDROBUTYRINE'>MDH</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1ZN:(2S,3S,4E,6E,8S,9S)-3-AMINO-9-METHOXY-2,6,8-TRIMETHYL-10-PHENYLDECA-4,6-DIENOIC+ACID'>1ZN</scene>, <scene name='pdbligand=ACB:3-METHYL-BETA-D-ASPARTIC+ACID'>ACB</scene>, <scene name='pdbligand=AZI:AZIDE+ION'>AZI</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FGA:GAMMA-D-GLUTAMIC+ACID'>FGA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MDH:N-METHYLDEHYDROBUTYRINE'>MDH</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1jk7|1jk7]], [[1it6|1it6]], [[1fjm|1fjm]], [[2bcd|2bcd]], [[3e7b|3e7b]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP1CA, PPP1A ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span></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=3e7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7a OCA], [https://pdbe.org/3e7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7a RCSB], [https://www.ebi.ac.uk/pdbsum/3e7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7a ProSAT]</span></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=3e7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3e7a OCA], [https://pdbe.org/3e7a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3e7a RCSB], [https://www.ebi.ac.uk/pdbsum/3e7a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3e7a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PP1A_HUMAN PP1A_HUMAN]] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.<ref>PMID:17283141</ref>
| + | [https://www.uniprot.org/uniprot/PP1A_HUMAN PP1A_HUMAN] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.<ref>PMID:17283141</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Nodularia spumigena]] |
| - | [[Category: Kelker, M S]] | + | [[Category: Kelker MS]] |
| - | [[Category: Page, R]] | + | [[Category: Page R]] |
| - | [[Category: Peti, W]] | + | [[Category: Peti W]] |
| - | [[Category: Carbohydrate metabolism]]
| + | |
| - | [[Category: Cell cycle]]
| + | |
| - | [[Category: Cell division]]
| + | |
| - | [[Category: Glycogen metabolism]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Iron]]
| + | |
| - | [[Category: Manganese]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein phosphatase]]
| + | |
| Structural highlights
3e7a is a 4 chain structure with sequence from Homo sapiens and Nodularia spumigena. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.63Å |
| Ligands: | , , , , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
PP1A_HUMAN Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Protein phosphatase 1 occurs in all tissues and regulates many pathways, ranging from cell-cycle progression to carbohydrate metabolism. Many naturally occurring, molecular toxins modulate PP1 activity, though the exact mechanism of this differential regulation is not understood. A detailed elucidation of these interactions is crucial for understanding the cellular basis of phosphatase function and signaling pathways but, more importantly, they can serve as the basis for highly specific therapeutics, e.g. against cancer. We report the crystal structures of PP1 in complex with nodularin-R at 1.63 A and tautomycin at 1.70 A resolution. The PP1:nodularin-R complex was used to demonstrate the utility of our improved PP1 production technique, which produces highly active, soluble PP1. Tautomycin is one of the few toxins that reportedly preferentially binds PP1>PP2A. Therefore, the PP1:tautomycin structure is the first complex structure with a toxin with preferred PP1 specificity. Furthermore, since tautomycin is a linear non-peptide-based toxin, our reported structure will aid the design of lead compounds for novel PP1-specific pharmaceuticals.
Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: a novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors.,Kelker MS, Page R, Peti W J Mol Biol. 2009 Jan 9;385(1):11-21. Epub 2008 Nov 1. PMID:18992256[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mi J, Guo C, Brautigan DL, Larner JM. Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res. 2007 Feb 1;67(3):1082-9. PMID:17283141 doi:10.1158/0008-5472.CAN-06-3071
- ↑ Kelker MS, Page R, Peti W. Crystal structures of protein phosphatase-1 bound to nodularin-R and tautomycin: a novel scaffold for structure-based drug design of serine/threonine phosphatase inhibitors. J Mol Biol. 2009 Jan 9;385(1):11-21. Epub 2008 Nov 1. PMID:18992256 doi:10.1016/j.jmb.2008.10.053
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