Summary information and primary citation
- PDB-id
-
6wru;
DSSR-derived features in text and
JSON formats
- Class
- ribosome
- Method
- cryo-EM (3.1 Å)
- Summary
- Structure of the 50s subunit of the ribosome from
methicillin resistant staphylococcus aureus in complex with
an isomer of the tedizolid
- Reference
-
Wright A, Deane-Alder K, Marschall E, Bamert R, Venugopal
H, Lithgow T, Lupton DW, Belousoff MJ (2020): "Characterization
of the Core Ribosomal Binding Region for the Oxazolidone
Family of Antibiotics Using Cryo-EM." Acs
Pharmacol Transl Sci, 3, 425-432.
doi: 10.1021/acsptsci.0c00041.
- 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 <i>Staphylococcus
aureus</i>. The ribosome-antibiotic complexes were
resolved to a resolution of around 3 Å enabling unambiguous
assignment of how each antibiotic interacts with the
PTC.
