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Nucleic Acids Research, volume 45, issue 16, pages 9573-9582

Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins

Almutairi Mashal M. 1
Svetlov Maxim S 1
Hansen Douglas A 2
Klepacki Dorota 1
Kang Han-Young 4
Sherman David M. 5
1
 
Center for Biomolecular Sciences, University of Illinois, Chicago, IL 60607, USA
2
 
Life Sciences Institute, University of Michigan, Ann Arbor, MI-48109, USA.
3
 
Dept. of Biological Sciences, Univ. of Illinois at Chicago, Chicago, IL 60607, USA.
4
 
Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361‐763, Republic of Korea
5
 
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
6
 
Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA.
Publication typeJournal Article
Publication date2017-07-29
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor14.9
ISSN03051048, 13624962
PubMed ID:  28934499
Genetics
Abstract
Abstract Antibiotics methymycin (MTM) and pikromycin (PKM), co-produced by Streptomyces venezuelae, represent minimalist macrolide protein synthesis inhibitors. Unlike other macrolides, which carry several side chains, a single desosamine sugar is attached to the macrolactone ring of MTM and PKM. In addition, the macrolactone scaffold of MTM is smaller than in other macrolides. The unusual structure of MTM and PKM and their simultaneous secretion by S. venezuelae bring about the possibility that two compounds would bind to distinct ribosomal sites. However, by combining genetic, biochemical and crystallographic studies, we demonstrate that MTM and PKM inhibit translation by binding to overlapping sites in the ribosomal exit tunnel. Strikingly, while MTM and PKM readily arrest the growth of bacteria, ∼40% of cellular proteins continue to be synthesized even at saturating concentrations of the drugs. Gel electrophoretic analysis shows that compared to other ribosomal antibiotics, MTM and PKM prevent synthesis of a smaller number of cellular polypeptides illustrating a unique mode of action of these antibiotics.

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GOST Copy
Almutairi M. M. et al. Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins // Nucleic Acids Research. 2017. Vol. 45. No. 16. pp. 9573-9582.
GOST all authors (up to 50) Copy
Almutairi M. M., Svetlov M. S., Hansen D. A., Khabibullina N. F., Klepacki D., Kang H., Sherman D. M., Vázquez Laslop N., Polikanov Y. S., Mankin A. S. Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins // Nucleic Acids Research. 2017. Vol. 45. No. 16. pp. 9573-9582.
RIS |
Cite this
RIS Copy
TY - JOUR
DO - 10.1093/nar/gkx673
UR - https://doi.org/10.1093%2Fnar%2Fgkx673
TI - Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins
T2 - Nucleic Acids Research
AU - Almutairi, Mashal M.
AU - Klepacki, Dorota
AU - Polikanov, Yury S
AU - Mankin, Alexander S.
AU - Svetlov, Maxim S
AU - Hansen, Douglas A
AU - Khabibullina, Nelli F
AU - Kang, Han-Young
AU - Sherman, David M.
AU - Vázquez Laslop, Nora
PY - 2017
DA - 2017/07/29 00:00:00
PB - Oxford University Press
SP - 9573-9582
IS - 16
VL - 45
PMID - 28934499
SN - 0305-1048
SN - 1362-4962
ER -
BibTex |
Cite this
BibTex Copy
@article{2017_Almutairi
author = {Mashal M. Almutairi and Dorota Klepacki and Yury S Polikanov and Alexander S. Mankin and Maxim S Svetlov and Douglas A Hansen and Nelli F Khabibullina and Han-Young Kang and David M. Sherman and Nora Vázquez Laslop},
title = {Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins},
journal = {Nucleic Acids Research},
year = {2017},
volume = {45},
publisher = {Oxford University Press},
month = {jul},
url = {https://doi.org/10.1093%2Fnar%2Fgkx673},
number = {16},
pages = {9573--9582},
doi = {10.1093/nar/gkx673}
}
MLA
Cite this
MLA Copy
Almutairi, Mashal M., et al. “Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins.” Nucleic Acids Research, vol. 45, no. 16, Jul. 2017, pp. 9573-9582. https://doi.org/10.1093%2Fnar%2Fgkx673.
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