Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate
| Autor: | Søren Molin, Ruggero La Rosa, Y. Halfon, Matthew J. Belousoff, Ada Yonath, Rocio Espinosa Portero, Donna Matzov, Z. Eyal, Anat Bashan, Helle Krogh Johansen, Alicia Jiménez-Fernández, Ella Zimmerman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
Modern medicine Multidisciplinary Aminoglycoside 030306 microbiology Chemistry Resistance Antibiotic Translation (biology) Ribosomal RNA Genetic code Ribosome Cystic fibrosis 3. Good health 03 medical and health sciences Biochemistry Ribosomal protein Protein biosynthesis 030304 developmental biology |
| Zdroj: | Halfon, Y, Jimenez-Fernandez, A, La Rosa, R, Espinosa Portero, R, Krogh Johansen, H, Matzov, D, Eyal, Z, Bashan, A, Zimmerman, E, Belousoff, M, Molin, S & Yonath, A 2019, ' Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate ', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 44, pp. 22275-22281 . https://doi.org/10.1073/pnas.1909831116 Halfon, Y, Jimenez-Fernandez, A, Rosa, R L, Portero, R E, Johansen, H K, Matzov, D, Eyal, Z, Bashan, A, Zimmerman, E, Belousoff, M, Molin, S & Yonath, A 2019, ' Structure of Pseudomonas aeruginosa ribosomes from an aminoglycoside-resistant clinical isolate ', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 44, pp. 22275-22281 . https://doi.org/10.1073/pnas.1909831116 |
| Popis: | Resistance to antibiotics has become a major threat to modern medicine. The ribosome plays a fundamental role in cell vitality by the translation of the genetic code into proteins; hence, it is a major target for clinically useful antibiotics. We report here the cryo-electron microscopy structures of the ribosome of a pathogenic aminoglycoside (AG)-resistant Pseudomonas aeruginosa strain, as well as of a nonresistance strain isolated from a cystic fibrosis patient. The structural studies disclosed defective ribosome complex formation due to a conformational change of rRNA helix H69, an essential intersubunit bridge, and a secondary binding site of the AGs. In addition, a stable conformation of nucleotides A1486 and A1487, pointing into helix h44, is created compared to a non-AG-bound ribosome. We suggest that altering the conformations of ribosomal protein uL6 and rRNA helix H69, which interact with initiation-factor IF2, interferes with proper protein synthesis initiation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|