3pgl: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(2 intermediate revisions by the same user not shown)
Line 1: Line 1:


==Crystal structure of human small C-terminal domain phosphatase 1 (Scp1) bound to rabeprazole==
==Crystal structure of human small C-terminal domain phosphatase 1 (Scp1) bound to rabeprazole==
<StructureSection load='3pgl' size='340' side='right' caption='[[3pgl]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
<StructureSection load='3pgl' size='340' side='right'caption='[[3pgl]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3pgl]] is a 2 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=3PGL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PGL FirstGlance]. <br>
<table><tr><td colspan='2'>[[3pgl]] is a 2 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=3PGL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PGL 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>, <scene name='pdbligand=RZX:2-[(R)-{[4-(3-METHOXYPROPOXY)-3-METHYLPYRIDIN-2-YL]METHYL}SULFINYL]-1H-BENZIMIDAZOLE'>RZX</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]] 2.35&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l0b|3l0b]], [[3l0c|3l0c]], [[3l0y|3l0y]], [[2ghq|2ghq]], [[2ght|2ght]], [[1t9z|1t9z]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RZX:2-[(R)-{[4-(3-METHOXYPROPOXY)-3-METHYLPYRIDIN-2-YL]METHYL}SULFINYL]-1H-BENZIMIDAZOLE'>RZX</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CTDSP1, CTDSP1 or SCP1, NIF3, NLIIF, SCP1 ([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=3pgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pgl OCA], [https://pdbe.org/3pgl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pgl RCSB], [https://www.ebi.ac.uk/pdbsum/3pgl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pgl 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>
<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=3pgl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pgl OCA], [http://pdbe.org/3pgl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3pgl RCSB], [http://www.ebi.ac.uk/pdbsum/3pgl PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3pgl ProSAT]</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;">
== Publication Abstract from PubMed ==
The unstructured C-terminal domain (CTD) of eukaryotic RNA polymerase II dynamically regulates the process of transcription by recruiting different factors to nascent mRNA through its multiple phosphorylation patterns. A newly discovered class of phosphatases, the human small C-terminal domain phosphatases (Scp's), specifically dephosphorylates phosphorylated Ser(5) (phospho.Ser(5)) of the tandem heptad repeats of the CTD of RNA polymerase II. Scp's also function as transcription regulators that epigenetically silence the expression of specific neuronal genes, whose inactivation leads to neuronal stem cell differentiation. Small molecule inhibitors of Scp's will be valuable for elucidating their mechanism in nervous system development and can possibly offer new strategies to treat diseases related to neurodegeneration. Despite the difficulty in developing selective inhibitors of protein phosphatases, we have recognized a characteristic hydrophobic binding pocket adjacent to the active site in Scp's that may facilitate selective inhibition. In the present study, we successfully identified the first selective lead compound, rabeprazole, for the Scp/TFIIF-interacting CTD phosphatase (Fcp) family. The high-resolution crystal structure of rabeprazole-bound Scp1 showed that the compound indeed binds to the hydrophobic binding pocket. We further confirmed that rabeprazole only targets Scp's but not its close family members Fcp1 and Dullard or bacteriophage lambda Ser/Thr phosphatase. Such specificity may prove important for In Vivo studies since accidental inhibition of Fcp1 or Dullard would result in cell malfunctions and even cell death.
 
Selective Inactivation of a Human Neuronal Silencing Phosphatase by a Small Molecule Inhibitor.,Zhang M, Cho EJ, Burstein G, Siegel D, Zhang Y ACS Chem Biol. 2011 Feb 24. PMID:21348431<ref>PMID:21348431</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pgl" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[RNA polymerase|RNA polymerase]]
*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Phosphoprotein phosphatase]]
[[Category: Large Structures]]
[[Category: Burstein, G]]
[[Category: Burstein G]]
[[Category: Cho, E J]]
[[Category: Cho EJ]]
[[Category: Siegel, D]]
[[Category: Siegel D]]
[[Category: Zhang, M]]
[[Category: Zhang M]]
[[Category: Zhang, Y]]
[[Category: Zhang Y]]
[[Category: Ctd phosphatase]]
[[Category: Had family]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Insertion domain]]
[[Category: Neuronal silencer]]

Latest revision as of 13:40, 21 February 2024

Crystal structure of human small C-terminal domain phosphatase 1 (Scp1) bound to rabeprazoleCrystal structure of human small C-terminal domain phosphatase 1 (Scp1) bound to rabeprazole

Structural highlights

3pgl is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.35Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

See Also

References

  1. ↑ 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
  2. ↑ 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

3pgl, resolution 2.35Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=3pgl&oldid=4067281"