2ghq: Difference between revisions

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New page: left|200px<br /> <applet load="2ghq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ghq, resolution 2.05Å" /> '''CTD-specific phosph...
 
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[[Image:2ghq.gif|left|200px]]<br />
[[Image:2ghq.gif|left|200px]]<br /><applet load="2ghq" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="2ghq" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="2ghq, resolution 2.05&Aring;" />
caption="2ghq, resolution 2.05&Aring;" />
'''CTD-specific phosphatase Scp1 in complex with peptide C-terminal domain of RNA polymerase II'''<br />
'''CTD-specific phosphatase Scp1 in complex with peptide C-terminal domain of RNA polymerase II'''<br />


==Overview==
==Overview==
Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of, RNA polymerase II (Pol II) represent a critical regulatory checkpoint for, transcription. Transcription initiation requires Fcp1/Scp1-mediated, dephosphorylation of phospho-CTD. Fcp1 and Scp1 belong to a family of Mg2+, -dependent phosphoserine (P.Ser)/phosphothreonine (P.Thr)-specific, phosphatases. We recently showed that Scp1 is an evolutionarily conserved, regulator of neuronal gene silencing. Here, we present the X-ray crystal, structures of a dominant-negative form of human Scp1 (D96N mutant) bound, to mono- and diphosphorylated peptides encompassing the CTD heptad repeat, (Y1S2P3T4S5P6S7). Moreover, kinetic and thermodynamic analyses of, Scp1-phospho-CTD peptide complexes support the structures determined. This, combined structure-function analysis discloses the residues in Scp1, involved in CTD binding and its preferential dephosphorylation of P.Ser5, of the CTD heptad repeat. Moreover, these results provide a template for, the design of specific inhibitors of Scp1 for the study of neuronal stem, cell development.
Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. Fcp1 and Scp1 belong to a family of Mg2+ -dependent phosphoserine (P.Ser)/phosphothreonine (P.Thr)-specific phosphatases. We recently showed that Scp1 is an evolutionarily conserved regulator of neuronal gene silencing. Here, we present the X-ray crystal structures of a dominant-negative form of human Scp1 (D96N mutant) bound to mono- and diphosphorylated peptides encompassing the CTD heptad repeat (Y1S2P3T4S5P6S7). Moreover, kinetic and thermodynamic analyses of Scp1-phospho-CTD peptide complexes support the structures determined. This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat. Moreover, these results provide a template for the design of specific inhibitors of Scp1 for the study of neuronal stem cell development.


==About this Structure==
==About this Structure==
2GHQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2GHQ OCA].  
2GHQ is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GHQ OCA].  


==Reference==
==Reference==
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[[Category: Phosphoprotein phosphatase]]
[[Category: Phosphoprotein phosphatase]]
[[Category: Protein complex]]
[[Category: Protein complex]]
[[Category: Noel, J.P.]]
[[Category: Noel, J P.]]
[[Category: Zhang, Y.]]
[[Category: Zhang, Y.]]
[[Category: MG]]
[[Category: MG]]
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[[Category: protein-peptide complex]]
[[Category: protein-peptide complex]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:18:58 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:31:49 2008''

Revision as of 18:31, 21 February 2008

File:2ghq.gif


2ghq, resolution 2.05Å

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CTD-specific phosphatase Scp1 in complex with peptide C-terminal domain of RNA polymerase II

OverviewOverview

Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. Fcp1 and Scp1 belong to a family of Mg2+ -dependent phosphoserine (P.Ser)/phosphothreonine (P.Thr)-specific phosphatases. We recently showed that Scp1 is an evolutionarily conserved regulator of neuronal gene silencing. Here, we present the X-ray crystal structures of a dominant-negative form of human Scp1 (D96N mutant) bound to mono- and diphosphorylated peptides encompassing the CTD heptad repeat (Y1S2P3T4S5P6S7). Moreover, kinetic and thermodynamic analyses of Scp1-phospho-CTD peptide complexes support the structures determined. This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat. Moreover, these results provide a template for the design of specific inhibitors of Scp1 for the study of neuronal stem cell development.

About this StructureAbout this Structure

2GHQ is a Protein complex structure of sequences from Homo sapiens with as ligand. Active as Phosphoprotein phosphatase, with EC number 3.1.3.16 Full crystallographic information is available from OCA.

ReferenceReference

Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1., Zhang Y, Kim Y, Genoud N, Gao J, Kelly JW, Pfaff SL, Gill GN, Dixon JE, Noel JP, Mol Cell. 2006 Dec 8;24(5):759-70. PMID:17157258

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