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Structures of the S...
Structures of the Staphylococcus aureus ribosome inhibited by fusidic acid and fusidic acid cyclopentane
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- González-López, Adrián (författare)
- Uppsala universitet,Strukturbiologi,Selmer
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- Larsson, Daniel S. D. (författare)
- Uppsala universitet,Strukturbiologi
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- Koripella, Ravi Kiran (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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Cain, Brett N. (författare)
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Garcia Chavez, Martin (författare)
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Hergenrother, Paul J. (författare)
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- Sanyal, Suparna (författare)
- Uppsala universitet,Molekylärbiologi
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- Selmer, Maria (författare)
- Uppsala universitet,Strukturbiologi
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(creator_code:org_t)
- Springer Nature, 2024
- 2024
- Engelska.
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://uu.diva-port...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The antibiotic fusidic acid (FA) is used to treat Staphylococcus aureus infections. It inhibits protein synthesis by binding to elongation factor G (EF-G) and preventing its release from the ribosome after translocation. While FA, due to permeability issues, is only effective against gram-positive bacteria, the available structures of FA-inhibited complexes are from gram-negative model organisms. To fill this knowledge gap, we solved cryo-EM structures of the S. aureus ribosome in complex with mRNA, tRNA, EF-G and FA to 2.5 Å resolution and the corresponding complex structures with the recently developed FA derivative FA-cyclopentane (FA-CP) to 2.0 Å resolution. With both FA variants, the majority of the ribosomal particles are observed in chimeric state and only a minor population in post-translocational state. As expected, FA binds in a pocket between domains I, II and III of EF-G and the sarcin-ricin loop of 23S rRNA. FA-CP binds in an identical position, but its cyclopentane moiety provides additional contacts to EF-G and 23S rRNA, suggesting that its improved resistance profile towards mutations in EF-G is due to higher-affinity binding. These high-resolution structures reveal new details about the S. aureus ribosome, including confirmation of many rRNA modifications, and provide an optimal starting point for future structure-based drug discovery on an important clinical drug target.
Ämnesord
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- Fusidic acid
- Ribosome
- EF-G
- Cryo-EM
- Elongation factor G
- Biology with specialization in Structural Biology
- Biologi med inriktning mot strukturbiologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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