7NHL

VgaA-LC, an antibiotic resistance ABCF, in complex with 70S ribosome from Staphylococcus aureus

これはPDB形式変換不可エントリーです。

7NHL の概要

• エントリーDOI: 10.2210/pdb7nhl/pdb
• EMDBエントリー: 12332
• 分子名称: Lincosamide-streptogramin A resistance protein, 50S ribosomal protein L4, 50S ribosomal protein L5, ... (57 entities in total)
• 機能のキーワード: antibiotic resistance element, abcf, antibiotic resistance, atpase, protein synthesis, ribosome
• 由来する生物種: Staphylococcus haemolyticus; 詳細
• タンパク質・核酸の鎖数: 53
• 化学式量合計: 2231635.24

構造登録者

Crowe-McAuliffe, C.,Murina, V.,Hauryliuk, V.,Wilson, D.N. (登録日: 2021-02-10, 公開日: 2021-05-05, 最終更新日: 2024-05-01)

主引用文献

Crowe-McAuliffe, C.,Murina, V.,Turnbull, K.J.,Kasari, M.,Mohamad, M.,Polte, C.,Takada, H.,Vaitkevicius, K.,Johansson, J.,Ignatova, Z.,Atkinson, G.C.,O'Neill, A.J.,Hauryliuk, V.,Wilson, D.N.
Structural basis of ABCF-mediated resistance to pleuromutilin, lincosamide, and streptogramin A antibiotics in Gram-positive pathogens.
Nat Commun, 12:3577-3577, 2021

PubMed Abstract: Target protection proteins confer resistance to the host organism by directly binding to the antibiotic target. One class of such proteins are the antibiotic resistance (ARE) ATP-binding cassette (ABC) proteins of the F-subtype (ARE-ABCFs), which are widely distributed throughout Gram-positive bacteria and bind the ribosome to alleviate translational inhibition from antibiotics that target the large ribosomal subunit. Here, we present single-particle cryo-EM structures of ARE-ABCF-ribosome complexes from three Gram-positive pathogens: Enterococcus faecalis LsaA, Staphylococcus haemolyticus VgaA and Listeria monocytogenes VgaL. Supported by extensive mutagenesis analysis, these structures enable a general model for antibiotic resistance mediated by these ARE-ABCFs to be proposed. In this model, ABCF binding to the antibiotic-stalled ribosome mediates antibiotic release via mechanistically diverse long-range conformational relays that converge on a few conserved ribosomal RNA nucleotides located at the peptidyltransferase center. These insights are important for the future development of antibiotics that overcome such target protection resistance mechanisms.

PubMed: 34117249
DOI: 10.1038/s41467-021-23753-1

実験手法

ELECTRON MICROSCOPY (3.1 Å)