6ddd | pdb_00006ddd

Structure of the 50S ribosomal subunit from Methicillin Resistant Staphylococcus aureus in complex with the oxazolidinone antibiotic LZD-5

Loading... Status: waiting for Mol* initialization Structural highlights 6ddd is a 10 chain structure with sequence from Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.1Å Ligands: G6V Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RL13_STAA8 This protein is one of the early assembly proteins of the 50S ribosomal subunit, although it is not seen to bind rRNA by itself. It is important during the early stages of 50S assembly. Publication Abstract from PubMed While 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ribosome 3D structures

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