6nd6
From Proteopedia
Crystal structure of the Thermus thermophilus 70S ribosome in complex with erythromycin and bound to mRNA and A-, P-, and E-site tRNAs at 2.85A resolution
Structural highlights
FunctionRL4_THET8 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 (By similarity).[HAMAP-Rule:MF_01328_B] Forms part of the polypeptide exit tunnel (By similarity).[HAMAP-Rule:MF_01328_B] This protein can be incorporated into E.coli ribosomes in vivo, which resulted in decreased peptidyltransferase (Ptase) activity of the hybrid ribosomes. The hybrid 50S subunits associate less well with 30S subunits to form the ribosome.[HAMAP-Rule:MF_01328_B] Publication Abstract from PubMedThe 70S ribosome is a major target for antibacterial drugs. Two of the classical antibiotics, chloramphenicol (CHL) and erythromycin (ERY), competitively bind to adjacent but separate sites on the bacterial ribosome: the catalytic peptidyl transferase center (PTC) and the nascent polypeptide exit tunnel (NPET), respectively. The previously reported competitive binding of CHL and ERY might be due either to a direct collision of the two drugs on the ribosome or due to a drug-induced allosteric effect. Because of the resolution limitations, the available structures of these antibiotics in complex with bacterial ribosomes do not allow us to discriminate between these two possible mechanisms. In this work, we have obtained two crystal structures of CHL and ERY in complex with the Thermus thermophilus 70S ribosome at a higher resolution (2.65A and 2.89A, respectively) allowing unambiguous placement of the drugs in the electron density maps. Our structures provide evidence of the direct collision of CHL and ERY on the ribosome, which rationalizes the observed competition between the two drugs. High-resolution crystal structures of ribosome-bound chloramphenicol and erythromycin provide the ultimate basis for their competition.,Svetlov MS, Plessa E, Chen CW, Bougas A, Krokidis MG, Dinos GP, Polikanov Y RNA. 2019 Feb 7. pii: rna.069260.118. doi: 10.1261/rna.069260.118. PMID:30733327[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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