کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1953314 1057264 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Two nucleotide substitutions in the A-site of yeast 18S rRNA affect translation and differentiate the interaction of ribosomes with aminoglycoside antibiotics
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Two nucleotide substitutions in the A-site of yeast 18S rRNA affect translation and differentiate the interaction of ribosomes with aminoglycoside antibiotics
چکیده انگلیسی

Two mutations in the A-site of 18S rRNA of Saccharomyces cerevisiae were investigated. The first, A1491G (rdn15), creates in yeast the same C1409–G1491 base pair as in Escherichia coli and has behaved as an antisuppressor in genetic studies. Ribosomes from rdn15 are error-restrictive but their peptidyltransferase activity remains unchanged. The second mutation, U1495C (rdnhyg1), was initially isolated as a hygromycin-resistant mutation in Tetrahymena thermophila. We show that rdnhyg1 ribosomes are slightly error prone. Mutation rdnhyg1 does not affect catalytic activity, but it affects translocation, confirming the importance of nucleotide 1495 in the ratchet-like movement of the two subunits during translation. Paromomycin, an aminoglycoside antibiotic that binds to the ribosomal A-site, induces translational misreading and causes sensitivity to yeast cells. Mutation rdn15 is shown to be highly sensitive to both effects of paromomycin, while mutation rdnhyg1 is relatively resistant. Tobramycin, another aminoglycoside, does not affect the growth of yeast cells. Like paromomycin, however, it increases the error rate in rdn15 ribosomes relative to wild-type and decreases it in rdnhyg1 ribosomes. These mutations help define the role of two crucial sites in ribosome function and distinguish the modes of action of two aminoglycosides, a useful fact in the search for new strategies in drug design.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 90, Issue 6, June 2008, Pages 908–917
نویسندگان
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