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| | ==Structure of Human Scp1 bound to cis-proline peptidomimetic CTD phospho-Ser5 peptide== | | ==Structure of Human Scp1 bound to cis-proline peptidomimetic CTD phospho-Ser5 peptide== |
| - | <StructureSection load='4yh1' size='340' side='right' caption='[[4yh1]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4yh1' size='340' side='right'caption='[[4yh1]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yh1]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YH1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YH1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yh1]] is a 4 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=4YH1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YH1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4CG:(1R,2Z)-2-[(2R)-2-AMINO-3-(PHOSPHONOOXY)PROPYLIDENE]CYCLOPENTANECARBOXYLIC+ACID'>4CG</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=4CG:(1R,2Z)-2-[(2R)-2-AMINO-3-(PHOSPHONOOXY)PROPYLIDENE]CYCLOPENTANECARBOXYLIC+ACID'>4CG</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=4yh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yh1 OCA], [https://pdbe.org/4yh1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yh1 RCSB], [https://www.ebi.ac.uk/pdbsum/4yh1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yh1 ProSAT]</span></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ygx|4ygx]], [[4ygy|4ygy]]</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=4yh1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yh1 OCA], [http://pdbe.org/4yh1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yh1 RCSB], [http://www.ebi.ac.uk/pdbsum/4yh1 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CTDS1_HUMAN CTDS1_HUMAN]] Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residues repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.<ref>PMID:12721286</ref> <ref>PMID:15681389</ref> | + | [https://www.uniprot.org/uniprot/CTDS1_HUMAN CTDS1_HUMAN] Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residues repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.<ref>PMID:12721286</ref> <ref>PMID:15681389</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Mayfield, J E]] | + | [[Category: Large Structures]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Complex]] | + | [[Category: Mayfield JE]] |
| - | [[Category: Hydrolase]] | + | [[Category: Zhang Y]] |
| - | [[Category: Peptidomimetic]]
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| - | [[Category: Phosphatase]]
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| Structural highlights
Function
CTDS1_HUMAN Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residues repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.[1] [2]
Publication Abstract from PubMed
Proline isomerization greatly impacts biological signaling but is subtle and difficult to detect in proteins. We characterize this poorly understood regulatory mechanism for RNA polymerase II carboxyl terminal domain (CTD) phosphorylation state using novel, direct, and quantitative chemical tools. We determine the proline isomeric preference of three CTD phosphatases: Ssu72 as cis-proline specific, Scp1 and Fcp1 as strongly trans-preferred. Due to this inherent characteristic, these phosphatases respond differently to enzymes that catalyze the isomerization of proline, like Ess1/Pin1. We demonstrate that this selective regulation of RNA polymerase II phosphorylation state exists within human cells, consistent with in vitro assays. These results support a model in which, instead of a global enhancement of downstream enzymatic activities, proline isomerases selectively boost the activity of a subset of CTD regulatory factors specific for cis-proline. This leads to diversified phosphorylation states of CTD in vitro and in cells. We provide the chemical tools to investigate proline isomerization and its ability to selectively enhance signaling in transcription and other biological contexts.
Chemical Tools To Decipher Regulation of Phosphatases by Proline Isomerization on Eukaryotic RNA Polymerase II.,Mayfield JE, Fan S, Wei S, Zhang M, Li B, Ellington AD, Etzkorn FA, Zhang YJ ACS Chem Biol. 2015 Sep 15. PMID:26332362[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yeo M, Lin PS, Dahmus ME, Gill GN. A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5. J Biol Chem. 2003 Jul 11;278(28):26078-85. Epub 2003 Apr 28. PMID:12721286 doi:10.1074/jbc.M301791200
- ↑ Yeo M, Lee SK, Lee B, Ruiz EC, Pfaff SL, Gill GN. Small CTD phosphatases function in silencing neuronal gene expression. Science. 2005 Jan 28;307(5709):596-600. PMID:15681389 doi:10.1126/science.1100801
- ↑ Mayfield JE, Fan S, Wei S, Zhang M, Li B, Ellington AD, Etzkorn FA, Zhang YJ. Chemical Tools To Decipher Regulation of Phosphatases by Proline Isomerization on Eukaryotic RNA Polymerase II. ACS Chem Biol. 2015 Sep 15. PMID:26332362 doi:http://dx.doi.org/10.1021/acschembio.5b00296
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