2ght: Difference between revisions

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New page: left|200px<br /> <applet load="2ght" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ght, resolution 1.8Å" /> '''CTD-specific phospha...
 
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[[Image:2ght.gif|left|200px]]<br />
[[Image:2ght.gif|left|200px]]<br /><applet load="2ght" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="2ght" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="2ght, resolution 1.8&Aring;" />
caption="2ght, resolution 1.8&Aring;" />
'''CTD-specific phosphatase Scp1 in complex with peptide from C-terminal domain of RNA polymerase II'''<br />
'''CTD-specific phosphatase Scp1 in complex with peptide from 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==
2GHT 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=2GHT OCA].  
2GHT 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=2GHT 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]]


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