6ddg
From Proteopedia
Structure of the 50S ribosomal subunit from Methicillin Resistant Staphylococcus aureus in complex with the oxazolidinone antibiotic LZD-6
Structural highlights
FunctionRL19_STAA8 This protein is located at the 30S-50S ribosomal subunit interface and may play a role in the structure and function of the aminoacyl-tRNA binding site. Publication Abstract from PubMedWhile the ribosome is a common target for antibiotics, challenges with crystallography can impede the development of new bioactives using structure-based drug design approaches. In this study we exploit common structural features present in linezolid-resistant forms of both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) to redesign the antibiotic. Enabled by rapid and facile cryoEM structures, this process has identified (S)-2,2-dichloro-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl) acetamide (LZD-5) and (S)-2-chloro-N-((3-(3-fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl) acetamide (LZD-6), which inhibit the ribosomal function and growth of linezolid-resistant MRSA and VRE. The strategy discussed highlights the potential for cryoEM to facilitate the development of novel bioactive materials. cryoEM-Guided Development of Antibiotics for Drug-Resistant Bacteria.,Belousoff MJ, Venugopal H, Wright A, Seoner S, Stuart I, Stubenrauch C, Bamert RS, Lupton DW, Lithgow T ChemMedChem. 2019 Mar 5;14(5):527-531. doi: 10.1002/cmdc.201900042. Epub 2019 Feb, 12. PMID:30667174[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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