Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit()

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 Therm...

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Detalles Bibliográficos
Autores principales: Tourigny, David S., Fernández, Israel S., Kelley, Ann C., Vakiti, Ramkrishna Reddy, Chattopadhyay, Amit Kumar, Dorich, Stéphane, Hanessian, Stephen, Ramakrishnan, V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2013
Materias:
Brevia
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3794158/
https://www.ncbi.nlm.nih.gov/pubmed/23702293
http://dx.doi.org/10.1016/j.jmb.2013.05.004
Descripción
Sumario: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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