Document Detail

A second catalytic metal ion in group I ribozyme.
MedLine Citation:
PMID:  9285596     Owner:  NLM     Status:  MEDLINE    
Although only a subset of protein enzymes depend on the presence of a metal ion for their catalytic function, all naturally occurring RNA enzymes require metal ions to stabilize their structure and for catalytic competence. In the self-splicing group I intron from Tetrahymena thermophila, several divalent metals can serve structural roles, but only Mg2+ and Mn2+ promote splice-site cleavage and exon ligation. A study of a ribozyme reaction analogous to 5'-splice-site cleavage by guanosine uncovered the first metal ion with a definitive role in catalysis. Substitution of the 3'-oxygen of the leaving group with sulphur resulted in a metal-specificity switch, indicating an interaction between the leaving group and the metal ion. Here we use 3'-(thioinosylyl)-(3'-->5')-uridine, IspU, as a substrate in a reaction that emulates exon ligation. Activity requires the addition of a thiophilic metal ion (Cd2+ or Mn2+), providing evidence for stabilization of the leaving group by a metal ion in that step of splicing. Based on the principle of microscopic reversibility, this metal ion activates the nucleophilic 3'-hydroxyl of guanosine in the first step of splicing, supporting the model of a two-metal-ion active site.
L B Weinstein; B C Jones; R Cosstick; T R Cech
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Nature     Volume:  388     ISSN:  0028-0836     ISO Abbreviation:  Nature     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-09-22     Completed Date:  1997-09-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  805-8     Citation Subset:  IM    
Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder 80309-0215, USA.
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MeSH Terms
Cadmium / metabolism
Manganese / metabolism
Metals / chemistry,  metabolism*
RNA, Catalytic / chemistry,  metabolism*
Sulfur / metabolism
Tetrahymena thermophila
Uridine / analogs & derivatives,  metabolism
Reg. No./Substance:
0/3'-thioinosylyl-(3',5')uridine; 0/Metals; 0/RNA, Catalytic; 58-96-8/Uridine; 7439-96-5/Manganese; 7440-43-9/Cadmium; 7704-34-9/Sulfur

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