EMD-27009

Single-particle
2.66 Å
EMD-27009 Deposition: 18/05/2022
Map released: 15/03/2023
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
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EMD-27009

Cutibacterium acnes 50S ribosomal subunit with P-site tRNA and Sarecycline bound in the local refined map

EMD-27009

Single-particle
2.66 Å
EMD-27009 Deposition: 18/05/2022
Map released: 15/03/2023
Last modified: 30/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Cutibacterium acnes, Escherichia coli
Sample: 50S subunit from 70S ribosome with mRNA, P-site tRNA and Sarecycline bound
Fitted models: 8cvm (Avg. Q-score: 0.565)

Deposition Authors: Lomakin IB , Devarkar SC , Bunick CG
Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism.
Lomakin IB , Devarkar SC , Patel S, Grada A , Bunick CG
(2023) Nucleic Acids Res , 51 , 2915 - 2930
PUBMED: 36864821
DOI: doi:10.1093/nar/gkad103
ISSN: 1362-4962
ASTM: NARHAD
Abstract:
Acne vulgaris is a chronic disfiguring skin disease affecting ∼1 billion people worldwide, often having persistent negative effects on physical and mental health. The Gram-positive anaerobe, Cutibacterium acnes is implicated in acne pathogenesis and is, therefore, a main target for antibiotic-based acne therapy. We determined a 2.8-Å resolution structure of the 70S ribosome of Cutibacterium acnes by cryogenic electron microscopy and discovered that sarecycline, a narrow-spectrum antibiotic against Cutibacterium acnes, may inhibit two active sites of this bacterium's ribosome in contrast to the one site detected previously on the model ribosome of Thermus thermophilus. Apart from the canonical binding site at the mRNA decoding center, the second binding site for sarecycline exists at the nascent peptide exit tunnel, reminiscent of the macrolides class of antibiotics. The structure also revealed Cutibacterium acnes-specific features of the ribosomal RNA and proteins. Unlike the ribosome of the Gram-negative bacterium Escherichia coli, Cutibacterium acnes ribosome has two additional proteins, bS22 and bL37, which are also present in the ribosomes of Mycobacterium smegmatis and Mycobacterium tuberculosis. We show that bS22 and bL37 have antimicrobial properties and may be involved in maintaining the healthy homeostasis of the human skin microbiome.