9JSR

50S precursor - Erm complex (C-I)

9JSR の概要

• エントリーDOI: 10.2210/pdb9jsr/pdb
• EMDBエントリー: 61781
• 分子名称: 50S ribosomal protein L32, 50S ribosomal protein L17, 50S ribosomal protein L19, ... (19 entities in total)
• 機能のキーワード: 50s precursor, erm, methyltransferase, antibiotic resistance, ribosome-protein complex, ribosome
• 由来する生物種: Escherichia coli K-12; 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 1173170.86

構造登録者

Sengupta, S.,Mukherjee, R.,Pilsl, M.,Bagale, S.,Adhikary, A.D.,Borkar, A.,Pradeepkumar, P.I.,Engel, C.,Chowdhury, A.,Kaushal, P.S.,Anand, R. (登録日: 2024-10-01, 公開日: 2025-10-29, 最終更新日: 2025-12-10)

主引用文献

Sengupta, S.,Mukherjee, R.,Pilsl, M.,Bagale, S.,Adhikary, A.D.,Borkar, A.N.,Pradeepkumar, P.I.,Engel, C.,Chowdhury, A.,Kaushal, P.S.,Anand, R.
Mechanistic insights into 50 S precursor recognition and targeting by erythromycin resistance methyltransferase.
Sci Adv, 11:eaea1545-eaea1545, 2025

PubMed Abstract: Erythromycin resistance methyltransferases (Erms) confer resistance to macrolide, lincosamide, and streptogramin B antibiotics by methylating an internal base (A2058, numbering) in an elusive precursor ribosomal state. Here, we capture the 50 ribosomal precursor-Erm complex by cryo-EM and show that a transient pocket formed in the early steps of ribosome biogenesis, situated 35 angstrom from the methylation site, serves as an anchor for the auxiliary C-terminal domain of Erm, thereby playing a crucial role in achieving specificity in this short-lived substrate with evolving structural features. Cryo-EM reveals that the catalytic Rossman fold of Erm undergoes a swaying motion to facilitate substrate scouting. Corroboratory smFRET studies show that for effective catalysis, Erm transitions between multiple conformations, an effective strategy adopted to orient the dynamic helix where methylation occurs. Unraveling this unique mechanism of targeting adopted by Erm paves the way for selective design of allosteric inhibitors directed toward reversing MLS resistance.

PubMed: 41296849
DOI: 10.1126/sciadv.aea1545

実験手法

ELECTRON MICROSCOPY (4 Å)