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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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
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author Tourigny, David S.
Fernández, Israel S.
Kelley, Ann C.
Vakiti, Ramkrishna Reddy
Chattopadhyay, Amit Kumar
Dorich, Stéphane
Hanessian, Stephen
Ramakrishnan, V.
author_facet Tourigny, David S.
Fernández, Israel S.
Kelley, Ann C.
Vakiti, Ramkrishna Reddy
Chattopadhyay, Amit Kumar
Dorich, Stéphane
Hanessian, Stephen
Ramakrishnan, V.
author_sort Tourigny, David S.
collection PubMed
description 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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spelling pubmed-37941582013-10-23 Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit() Tourigny, David S. Fernández, Israel S. Kelley, Ann C. Vakiti, Ramkrishna Reddy Chattopadhyay, Amit Kumar Dorich, Stéphane Hanessian, Stephen Ramakrishnan, V. J Mol Biol Brevia 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. Elsevier 2013-10-23 /pmc/articles/PMC3794158/ /pubmed/23702293 http://dx.doi.org/10.1016/j.jmb.2013.05.004 Text en © 2013 The Authors https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license
spellingShingle Brevia
Tourigny, David S.
Fernández, Israel S.
Kelley, Ann C.
Vakiti, Ramkrishna Reddy
Chattopadhyay, Amit Kumar
Dorich, Stéphane
Hanessian, Stephen
Ramakrishnan, V.
Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit()
title Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit()
title_full Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit()
title_fullStr Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit()
title_full_unstemmed Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit()
title_short Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit()
title_sort crystal structure of a bioactive pactamycin analog bound to the 30s ribosomal subunit()
topic Brevia
url 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
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