Structure and mechanism of the RNA triphosphatase component of mammalian mRNA capping enzyme Journal Article
| Authors: | Changela, A.; Ho, C. K.; Martins, A.; Shuman, S.; Mondragón, A. |
| Article Title: | Structure and mechanism of the RNA triphosphatase component of mammalian mRNA capping enzyme |
| Abstract: | The 5′ capping of mammalian pre-mRNAs is initiated by RNA triphosphatase, a member of the cysteine phosphatase superfamily. Here we report the 1.65 Å crystal structure of mouse RNA triphosphatase, which reveals a deep, positively charged active site pocket that can fit a 5′ triphosphate end. Structural, biochemical and mutational results show that despite sharing an HCxxxxxR(S/T) motif, a phosphoenzyme intermediate and a core α/β-fold with other cysteine phosphatases, the mechanism of phosphoanhydride cleavage by mammalian capping enzyme differs from that used by protein phosphatases to hydrolyze phosphomonoesters. The most significant difference is the absence of a carboxylate general acid catalyst in RNA triphosphatase. Residues conserved uniquely among the RNA phosphatase subfamily are important for function in cap formation and are likely to play a role in substrate recognition. |
| Keywords: | unclassified drug; animals; mice; phosphatase; rna triphosphatase; acid anhydride hydrolases; rna; amino acid sequence; molecular sequence data; sequence homology, amino acid; messenger rna; crystal structure; models, molecular; binding sites; catalysis; rna processing; mammals; enzyme structure; phosphate; hydrolysis; protein structure, secondary; mutagenesis; enzyme mechanism; mrna capping; rna capping; nucleotidyltransferases; cysteine derivative; phosphoanhydride; cysteine phosphatase; priority journal; article; capping phenomenon; phosphoester derivative |
| Journal Title: | EMBO Journal |
| Volume: | 20 |
| Issue: | 10 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2001-05-15 |
| Start Page: | 2575 |
| End Page: | 2586 |
| Language: | English |
| DOI: | 10.1093/emboj/20.10.2575 |
| PUBMED: | 11350947 |
| PROVIDER: | scopus |
| PMCID: | PMC125469 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work