8ev6

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

Structural highlights

8ev6 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 2.946Å
Ligands:0TD, 2MA, 2MG, 2MU, 4OC, 4SU, 5MC, 5MU, 7MG, AKN, M2G, MA6, MG, MIA, OMG, PSU, UR3, ZN
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RL2_THET8 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 (By similarity). Makes several contacts with the 16S rRNA (forming bridge B7b) in the 70S ribosome.[HAMAP-Rule:MF_01320_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.

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Citations
2 reviews cite this structure
Mechanistic Insights into Clinically Relevant Ribosome-Targeting Antibiotics.
Krawczyk et al. (2024)
1 more
1 other articles
No citations found

See Also

References

  1. ↑ 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

Contents


PDB ID 8ev6

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OCA

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