Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity Journal Article
| Authors: | Gu, M.; Fabrega, C.; Liu, S. W.; Liu, H.; Kiledjian, M.; Lima, C. D. |
| Article Title: | Insights into the structure, mechanism, and regulation of scavenger mRNA decapping activity |
| Abstract: | Complete removal of residual N-7 guanine cap from degraded messenger RNA is necessary to prevent accumulation of intermediates that might interfere with RNA processing, export, and translation. The human scavenger decapping enzyme, DcpS, catalyzes residual cap hydrolysis following mRNA degradation, releasing N-7 methyl guanosine monophosphate and 5′-diphosphate terminated cap or mRNA products. DcpS structures bound to m7GpppG or m 7GpppA reveal an asymmetric DcpS dimer that simultaneously creates an open nonproductive DcpS-cap complex and a closed productive DcpS-cap complex that alternate via 30 Å domain movements. Structural and biochemical analysis suggests an autoregulatory mechanism whereby premature decapping mRNA is prevented by blocking the conformational changes that are required to form a closed productive active site capable of cap hydrolysis. |
| Keywords: | unclassified drug; protein conformation; protein domain; animals; protein binding; molecular mechanics; regulatory mechanism; amino acid sequence; molecular sequence data; messenger rna; guanosine derivative; enzyme analysis; guanosine; rna caps; sequence alignment; models, molecular; dimerization; crystallography, x-ray; binding sites; catalysis; nucleic acid conformation; enzyme binding; enzyme structure; phosphate; hydrolysis; enzyme; rna degradation; endoribonucleases; dimer; methyl group; scavenger; humans; article; 5' diphosphate; human scavenger decapping enzyme; n 7 methylguanosine phosphate; pyrophosphoric acid derivative |
| Journal Title: | Molecular Cell |
| Volume: | 14 |
| Issue: | 1 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2004-04-09 |
| Start Page: | 67 |
| End Page: | 80 |
| Language: | English |
| DOI: | 10.1016/s1097-2765(04)00180-7 |
| PROVIDER: | scopus |
| PUBMED: | 15068804 |
| DOI/URL: | |
| Notes: | Mol. Cell -- Cited By (since 1996):63 -- Export Date: 16 June 2014 -- CODEN: MOCEF -- Source: Scopus |
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