1. Crystal structure of a bioactive pactamycin analog bound to the 30S ribosomal subunit.
- Author
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Tourigny DS, Fernández IS, Kelley AC, Vakiti RR, Chattopadhyay AK, Dorich S, Hanessian S, and Ramakrishnan V
- Subjects
- Antibiotics, Antineoplastic chemistry, Antibiotics, Antineoplastic metabolism, Crystallography, X-Ray, Models, Molecular, Molecular Conformation, Pactamycin analogs & derivatives, Protein Binding, RNA, Ribosomal, 16S chemistry, RNA, Ribosomal, 16S metabolism, Thermus thermophilus metabolism, Pactamycin chemistry, Pactamycin metabolism, Ribosome Subunits, Small, Bacterial chemistry, Ribosome Subunits, Small, Bacterial metabolism
- 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., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2013
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