2ghq
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, resolution 2.05Å | |||||||
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Ligands: | |||||||
Gene: | CTDSP1 (Homo sapiens) | ||||||
Activity: | Phosphoprotein phosphatase, with EC number 3.1.3.16 | ||||||
Coordinates: | save as pdb, mmCIF, xml |
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. 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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