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8ev7

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Crystal structure of the Thermus thermophilus 70S ribosome in complex with kanamycin, mRNA, and A-, P-, and E-site tRNAs

Structural highlights

8ev7 is a 20 chain structure with sequence from Thermus thermophilus HB8. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.89Å
Ligands:	, , , , , , , , , , , , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RL4_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 PubMed

Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of kanamycin, is commonly used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries the 4-amino-2-hydroxy butyrate (AHB) moiety at the N(1) amino group of the central 2-deoxystreptamine (2-DOS) ring, which may confer amikacin a unique ribosome inhibition profile. Here we use in vitro fast kinetics combined with X-ray crystallography and cryo-EM to dissect the mechanisms of ribosome inhibition by amikacin and the parent compound, kanamycin. Amikacin interferes with tRNA translocation, release factor-mediated peptidyl-tRNA hydrolysis, and ribosome recycling, traits attributed to the additional interactions amikacin makes with the decoding center. The binding site in the large ribosomal subunit proximal to the 3'-end of tRNA in the peptidyl (P) site lays the groundwork for rational design of amikacin derivatives with improved antibacterial properties.

Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome.,Seely SM, Parajuli NP, De Tarafder A, Ge X, Sanyal S, Gagnon MG Nat Commun. 2023 Aug 3;14(1):4666. doi: 10.1038/s41467-023-40416-5. PMID:37537169^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Seely SM, Parajuli NP, De Tarafder A, Ge X, Sanyal S, Gagnon MG. Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome. Nat Commun. 2023 Aug 3;14(1):4666. PMID:37537169 doi:10.1038/s41467-023-40416-5