Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by M Diver
Total Records ( 1 ) for M Diver
  N Keppetipola , R Jain , B Meineke , M Diver and S. Shuman
 

tRNA anticodon damage inflicted by secreted ribotoxins such as Kluyveromyces lactis -toxin and bacterial colicins underlies a rudimentary innate immune system that distinguishes self from nonself species. The intracellular expression of -toxin (a 232-amino acid polypeptide) arrests the growth of Saccharomyces cerevisiae by incising a single RNA phosphodiester 3' of the modified wobble base of tRNAGlu. Fungal -toxin bears no primary structure similarity to any known nuclease and has no plausible homologs in the protein database. To gain insight to -toxin's mechanism, we tested the effects of alanine mutations at 62 basic, acidic, and polar amino acids on ribotoxin activity in vivo. We thereby identified 22 essential residues, including 10 lysines, seven arginines, three glutamates, one cysteine, and one histidine (His209, the only histidine present in -toxin). Structure–activity relations were gleaned from the effects of 44 conservative substitutions. Recombinant tag-free -toxin, a monomeric protein, incised an oligonucleotide corresponding to the anticodon stem–loop of tRNAGlu at a single phosphodiester 3' of the wobble uridine. The anticodon nuclease was metal independent. RNA cleavage was abolished by ribose 2'-H and 2'-F modifications of the wobble uridine. Mutating His209 to alanine, glutamine, or asparagine abolished nuclease activity. We propose that -toxin catalyzes an RNase A-like transesterification reaction that relies on His209 and a second nonhistidine side chain as general acid–base catalysts.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility