8cvm
Cutibacterium acnes 50S ribosomal subunit with P-site tRNA and Sarecycline bound in the local refined map
Structural highlights
FunctionRL2_CUTAK One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome.[HAMAP-Rule:MF_01320] Publication Abstract from PubMedAcne vulgaris is a chronic disfiguring skin disease affecting approximately 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-A 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. Sarecycline inhibits protein translation in Cutibacterium acnes 70S ribosome using a two-site mechanism.,Lomakin IB, Devarkar SC, Patel S, Grada A, Bunick CG Nucleic Acids Res. 2023 Apr 11;51(6):2915-2930. doi: 10.1093/nar/gkad103. PMID:36864821[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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