The Structure of Fcp1, an Essential RNA Polymerase II CTD Phosphatase Journal Article
| Authors: | Ghosh, A.; Shuman, S.; Lima, C. D. |
| Article Title: | The Structure of Fcp1, an Essential RNA Polymerase II CTD Phosphatase |
| Abstract: | Kinases and phosphatases regulate mRNA synthesis and processing by phosphorylating and dephosphorylating the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. Fcp1 is an essential CTD phosphatase that preferentially hydrolyzes Ser2-PO4 of the tandem YSPTSPS CTD heptad array. Fcp1 crystal structures were captured at two stages of the reaction pathway: a Mg-BeF3 complex that mimics the aspartylphosphate intermediate and a Mg-AlF4- complex that mimics the transition state of the hydrolysis step. Fcp1 is a Y-shaped protein composed of an acylphosphatase domain located at the base of a deep canyon formed by flanking modules that are missing from the small CTD phosphatase (SCP) clade: an Fcp1-specific helical domain and a C-terminal BRCA1 C-terminal (BRCT) domain. The structure and mutational analysis reveals that Fcp1 and Scp1 (a Ser5-selective phosphatase) adopt different CTD-binding modes; we surmise the CTD threads through the Fcp1 canyon to access the active site. © 2008 Elsevier Inc. All rights reserved. |
| Keywords: | unclassified drug; mutation, missense; nonhuman; proteins; carboxy terminal sequence; protein binding; transcription, genetic; mutational analysis; phosphorylation; brca1 protein; rna; amino acid sequence; molecular sequence data; sequence homology, amino acid; saccharomyces cerevisiae; substrate specificity; crystal structure; hydrogen bonding; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; protein dephosphorylation; protein structure; rna polymerase ii; hydrolysis; protein structure, secondary; mutagenesis; phosphoprotein phosphatases; crystallography; consensus sequence; fcp1 protein; scp1 protein; repetitive sequences, amino acid |
| Journal Title: | Molecular Cell |
| Volume: | 32 |
| Issue: | 4 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2008-11-21 |
| Start Page: | 478 |
| End Page: | 490 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2008.09.021 |
| PUBMED: | 19026779 |
| PROVIDER: | scopus |
| PMCID: | PMC2645342 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 13" - "Export Date: 17 November 2011" - "CODEN: MOCEF" - "Source: Scopus" |
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