6WQN

Structure of the 50S subunit of the ribosome from Methicillin Resistant Staphylococcus aureus in complex with the antibiotic, contezolid

Summary for 6WQN

• Entry DOI: 10.2210/pdb6wqn/pdb
• EMDB information: 21872
• Descriptor: 50S ribosomal protein L19, 50S ribosomal protein L29, 50S ribosomal protein L3, ... (28 entities in total)
• Functional Keywords: antibiotic, contezolid, oxazolidinone, ribosome
• Biological source: Staphylococcus aureus; More
• Total number of polymer chains: 27
• Total formula weight: 1295957.02

Authors

Belousoff, M.J. (deposition date: 2020-04-29, release date: 2020-06-03, Last modification date: 2020-12-16)

Primary citation

Wright, A.,Deane-Alder, K.,Marschall, E.,Bamert, R.,Venugopal, H.,Lithgow, T.,Lupton, D.W.,Belousoff, M.J.
Characterization of the Core Ribosomal Binding Region for the Oxazolidone Family of Antibiotics Using Cryo-EM.
Acs Pharmacol Transl Sci, 3:425-432, 2020

PubMed Abstract: Linezolid and tedizolid are oxazolidinones with established clinical utility for the treatment of Gram-positive pathogens. Over time it has become apparent that even modest structural changes to the core phenyl oxazolidinone leads to drastic changes in biological activity. Consequently, the structure-activity relationship around the core oxazolidinone is constantly evolving, often reflected with new structural motifs present in nascent oxazolidinones. Herein we describe the use of cryo-electron microscopy to examine the differences in binding of several functionally different oxazolidinones in the hopes of enhanced understanding of their SAR. Tedizolid, radezolid, T145, and contezolid have been examined within the peptidyl transferase center (PTC) of the 50S ribosomal subunit from methicillin resistant . The ribosome-antibiotic complexes were resolved to a resolution of around 3 Å enabling unambiguous assignment of how each antibiotic interacts with the PTC.

PubMed: 32566908
DOI: 10.1021/acsptsci.0c00041

Experimental method

ELECTRON MICROSCOPY (2.9 Å)