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7NHK

LsaA, an antibiotic resistance ABCF, in complex with 70S ribosome from Enterococcus faecalis

This is a non-PDB format compatible entry.
Summary for 7NHK
Entry DOI10.2210/pdb7nhk/pdb
EMDB information12331
DescriptorABC-F type ribosomal protection protein Lsa(A), 5S rRNA, 50S ribosomal protein L2, ... (58 entities in total)
Functional Keywordsantibiotic resistance element, ribosomal protein, lsaa, abcf, target protection, antibiotic resistance, ribosome
Biological sourceEnterococcus faecalis
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Total number of polymer chains53
Total formula weight2232137.36
Authors
Crowe-McAuliffe, C.,Kasari, M.,Hauryliuk, V.H.,Wilson, D.N. (deposition date: 2021-02-10, release date: 2021-05-05, Last modification date: 2024-07-10)
Primary citationCrowe-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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.9 Å)
Structure validation

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