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Crystal structure of a bioactive pactamycin analog bound to the 30S ribosomal subunit.

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.

SUBMITTER: Tourigny DS

PROVIDER: S-EPMC3794158 | biostudies-other | 2013 Oct

REPOSITORIES: biostudies-other

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Crystal structure of a bioactive pactamycin analog bound to the 30S ribosomal subunit.

Tourigny David S DS Fernández Israel S IS Kelley Ann C AC Vakiti Ramkrishna Reddy RR Chattopadhyay Amit Kumar AK Dorich Stéphane S Hanessian Stephen S Ramakrishnan V V

Journal of molecular biology 20130520 20

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 ...[more]

PMID: 23702293

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