9C4G

Cutibacterium acnes 50S ribosomal subunit with Clindamycin bound

9C4G の概要

• エントリーDOI: 10.2210/pdb9c4g/pdb
• EMDBエントリー: 45185
• 分子名称: 50S ribosomal protein L2, Large ribosomal subunit protein bL17, 50S ribosomal protein L18, ... (35 entities in total)
• 機能のキーワード: ribosome, clindamycin, acne, antibiotic
• 由来する生物種: Cutibacterium acnes; 詳細
• タンパク質・核酸の鎖数: 31
• 化学式量合計: 1448521.53

構造登録者

Lomakin, I.B.,Devarkar, S.C.,Bunick, C.G. (登録日: 2024-06-04, 公開日: 2024-08-21, 最終更新日: 2025-03-19)

主引用文献

Lomakin, I.B.,Devarkar, S.C.,Grada, A.,Bunick, C.G.
Mechanistic Basis for the Translation Inhibition of Cutibacterium acnes by Clindamycin.
J Invest Dermatol., 144:2553-2561.e3, 2024

PubMed Abstract: Inflammation and the Gram-positive anaerobic bacterium Cutibacterium acnes, which is implicated in acne pathogenesis and pilosebaceous-unit inflammation, are the main targets of antibiotic-based therapy against acne vulgaris (acne). The most widely used antibiotics in acne therapy are tetracyclines, macrolides, and lincosamides. Unfortunately, C. acnes bacteria over the past several decades have demonstrated increased resistance to these antibiotics, particularly to clindamycin. The precise knowledge of how antibiotics interact with their clinical target is needed to overcome this problem. Toward this goal, we determined the structure of clindamycin in complex with the ribosome of C. acnes at 2.53 Å resolution using cryogenic electron microscopy. The galactose sugar moiety of clindamycin interacts with nucleotides of the 23S ribosomal RNA directly or through a conserved network of water-mediated interactions. Its propyl pyrrolidinyl group interacts with the 23S ribosomal RNA through van der Waals forces. Clindamycin binding to the C. acnes ribosome interferes with both: proper orientation of the aminoacyl group of the A-site bound transfer RNA that is needed for peptide bond formation and with the extension of the nascent peptide. Our data are important for advancing the understanding of antibiotic resistance and development of narrow-spectrum antibacterial drugs, which is an urgent need for contemporary antibiotic stewardship.

PubMed: 39122144
DOI: 10.1016/j.jid.2024.07.013

実験手法

ELECTRON MICROSCOPY (2.53 Å)