Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit |
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Authors: | David S Tourigny Israel S Fernández Ann C Kelley Ramkrishna Reddy Vakiti Amit Kumar Chattopadhyay Stéphane Dorich Stephen Hanessian V Ramakrishnan |
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Institution: | 1 Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK;2 Department of Chemistry, Universite de Montreal, Station Centre Ville, CP 6128, Montreal, QC, Canada H3C 3J7 |
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Abstract: | Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential antiprotozoal and antitumor drugs. Here, we report a 3.1-Å crystal structure of de-6-MSA-pactamycin bound to its target site on the Thermus thermophilus 30S ribosomal subunit. Although de-6-MSA-pactamycin lacks the MSA moiety, it shares the same binding site as pactamycin and induces a displacement of nucleic acid template bound at the E-site of the 30S. The structure highlights unique interactions between this pactamycin analog and the ribosome, which paves the way for therapeutic development of related compounds. |
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Keywords: | MSA methylsalicylyl |
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