6wqn | pdb_00006wqn
Structure of the 50S subunit of the ribosome from Methicillin Resistant Staphylococcus aureus in complex with the antibiotic, contezolid
Structural highlights
Function[W8U3W0_STAAU] One of the primary rRNA binding proteins, it binds directly near the 3'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01325][RuleBase:RU003906] [A0A077UGA7_STAAU] Binds to the 23S rRNA.[HAMAP-Rule:MF_01341][SAAS:SAAS00687840] [W8TRD5_STAAU] One of the proteins that surrounds the polypeptide exit tunnel on the outside of the subunit.[HAMAP-Rule:MF_01326] One of two assembly initiator proteins, it binds directly to the 5'-end of the 23S rRNA, where it nucleates assembly of the 50S subunit.[HAMAP-Rule:MF_01326] [A0A077W1J0_STAAU] One of the primary rRNA binding proteins. Required for association of the 30S and 50S subunits to form the 70S ribosome, for tRNA binding and peptide bond formation. It has been suggested to have peptidyltransferase activity; this is somewhat controversial. Makes several contacts with the 16S rRNA in the 70S ribosome.[HAMAP-Rule:MF_01320] [A0A077V4G0_STAAU] Binds 23S rRNA and is also seen to make contacts with the A and possibly P site tRNAs.[HAMAP-Rule:MF_01342][RuleBase:RU004414] [A0A077UVB6_STAAU] 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.[HAMAP-Rule:MF_00402][RuleBase:RU000559] [A0A166DK89_STAAU] Forms part of the polypeptide exit tunnel.[HAMAP-Rule:MF_01328] One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.[HAMAP-Rule:MF_01328] [W8TUB4_STAAU] One of the early assembly proteins it binds 23S rRNA. One of the proteins that surrounds the polypeptide exit tunnel on the outside of the ribosome. Forms the main docking site for trigger factor binding to the ribosome.[HAMAP-Rule:MF_01369] [A0A077VMP6_STAAU] Binds directly to 23S ribosomal RNA and is necessary for the in vitro assembly process of the 50S ribosomal subunit. It is not involved in the protein synthesizing functions of that subunit.[HAMAP-Rule:MF_00382][RuleBase:RU000560] [A0A077UUA0_STAAU] Binds to 23S rRNA. Forms part of two intersubunit bridges in the 70S ribosome.[HAMAP-Rule:MF_01367][RuleBase:RU003950] [A0A0E0VQU6_STAA5] This protein binds to 23S rRNA in the presence of protein L20.[HAMAP-Rule:MF_01363][RuleBase:RU000562] [W8TRE0_STAAU] This is one of the proteins that binds and probably mediates the attachment of the 5S RNA into the large ribosomal subunit, where it forms part of the central protuberance.[HAMAP-Rule:MF_01337] [W8TUE6_STAAU] 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.[HAMAP-Rule:MF_01366][RuleBase:RU003878][SAAS:SAAS00725369] [A0A077UKF9_STAAU] The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome.[HAMAP-Rule:MF_01331] This protein binds specifically to 23S rRNA; its binding is stimulated by other ribosomal proteins, e.g., L4, L17, and L20. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome.[HAMAP-Rule:MF_01331][RuleBase:RU004008] Publication Abstract from PubMedLinezolid 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 Staphylococcus aureus. The ribosome-antibiotic complexes were resolved to a resolution of around 3 A enabling unambiguous assignment of how each antibiotic interacts with the PTC. Characterization of the Core Ribosomal Binding Region for the Oxazolidone Family of Antibiotics Using Cryo-EM.,Wright A, Deane-Alder K, Marschall E, Bamert R, Venugopal H, Lithgow T, Lupton DW, Belousoff MJ ACS Pharmacol Transl Sci. 2020 May 13;3(3):425-432. doi:, 10.1021/acsptsci.0c00041. eCollection 2020 Jun 12. PMID:32566908[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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