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| METAL-ION CATALYSIS IN THE TETRAHYMENA RIBOZYME REACTION |
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| Author(s): PICCIRILLI JA, VYLE JS, CARUTHERS MH, CECH TR |
| Source: NATURE Volume: 361 Issue: 6407 Pages: 85-88 Published: JAN 7 1993 |
| Times Cited: 334 References: 39 |
| Abstract: ALL catalytic RNAs (ribozymes) require or are stimulated by divalent metal ions, but it has been difficult to separate the contribution of these metal ions to formation of the RNA tertiary structure1 from a more direct role in catalysis. The Tetrahymena ribozyme catalyses cleavage of exogenous RNA2,3 or DNA4,5 substrates with an absolute requirement for Mg2+ or Mn2+ (ref. 6). A DNA substrate, in which the bridging 3' oxygen atom at the cleavage site is replaced by sulphur, is cleaved by the ribozyme about 1,000 times more slowly than the corresponding unmodified DNA substrate when Mg2+ is present as the only divalent metal ion. But addition of Mn2+ or Zn2+ to the reaction relieves this negative effect, with the 3' S-P bond being cleaved nearly as fast as the 3' O-P bond. Considering that Mn2+ and Zn2+ coordinate sulphur more strongly than Mg2+ does7,8, these results indicate that the metal ion contributes directly to catalysis by coordination to the 3' oxygen atom in the transition state, presumably stabilizing the developing negative charge on the leaving group. We conclude that the Tetrahymena ribozyme is a metalloenzyme, with mechanistic similarities to several protein enzymes9-12. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV COLORADO, HOWARD HUGHES MED INST, BOULDER, CO 80309 USA
2. UNIV COLORADO, DEPT CHEM & BIOCHEM, BOULDER, CO 80309 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: KF718 |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |