4U26

Crystal structure of the E. coli ribosome bound to dalfopristin and quinupristin.

This is a non-PDB format compatible entry.

Summary for 4U26

• Entry DOI: 10.2210/pdb4u26/pdb
• Related PRD ID: PRD_000505
• Descriptor: 16S rRNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (58 entities in total)
• Functional Keywords: protein biosynthesis, ribosome, rna, transfer, exit, peptidyl, 30s, 70s, 16s, ribosomal subunit, antibiotic, streptogramin
• Biological source: Escherichia coli str. K-12 substr. MDS42; More
• Total number of polymer chains: 107
• Total formula weight: 4271293.30

Authors

Noeske, J.,Huang, J.,Olivier, N.B.,Giacobbe, R.A.,Zambrowski, M.,Cate, J.H.D. (deposition date: 2014-07-16, release date: 2014-07-30, Last modification date: 2024-07-10)

Primary citation

Noeske, J.,Huang, J.,Olivier, N.B.,Giacobbe, R.A.,Zambrowski, M.,Cate, J.H.
Synergy of streptogramin antibiotics occurs independently of their effects on translation.
Antimicrob.Agents Chemother., 58:5269-5279, 2014

PubMed Abstract: Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the Escherichia coli 70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation.

PubMed: 24957822
DOI: 10.1128/AAC.03389-14

Experimental method

X-RAY DIFFRACTION (2.8 Å)