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9G30

The structure of the Candida albicans ribosome with tRNA-fMet, mRNA, and compounds (GEN and MFQ) shows strong density for the A site tRNA

This is a non-PDB format compatible entry.
Summary for 9G30
Entry DOI10.2210/pdb9g30/pdb
Related8CQ7 8CQW 8CRE 8OEQ 9G1Z
EMDB information50990
Descriptor60S ribosomal protein L20, 18S rRNA, 40S ribosomal protein S0, ... (82 entities in total)
Functional Keywordscandida albicans, ribosome, mrna, mefloquine, geneticin g418
Biological sourceCandida albicans
More
Total number of polymer chains80
Total formula weight3146912.03
Authors
Kolosova, O.,Zgadzay, Y.,Jenner, L.B.,Guskov, A.,Yusupov, M. (deposition date: 2024-07-11, release date: 2025-04-23, Last modification date: 2025-05-07)
Primary citationKolosova, O.,Zgadzay, Y.,Stetsenko, A.,Sukhinina, A.P.,Atamas, A.,Validov, S.,Rogachev, A.,Usachev, K.,Jenner, L.,Dmitriev, S.E.,Yusupova, G.,Guskov, A.,Yusupov, M.
Mechanism of read-through enhancement by aminoglycosides and mefloquine.
Proc.Natl.Acad.Sci.USA, 122:e2420261122-e2420261122, 2025
Cited by
PubMed Abstract: Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of aminoglycosides, particularly in combination with stop-codon read-through enhancers, for developing drugs that can rescue the production of full-length proteins. Using X-ray crystallography and single-particle cryo-EM, we obtained structures of the eukaryotic ribosome in complexes with several aminoglycosides (geneticin G418, paromomycin, and hygromycin B) and the antimalarial drug mefloquine (MFQ), which has also been identified as a read-through enhancer. Our study reveals a binding site of MFQ, which holds significant promise for the development of therapies targeting premature termination codon-related genetic and oncological diseases. The results underscore the crucial role of the bridge B7b/c in mediating the effects of MFQ on subunit rotation dynamics. Through a comprehensive analysis of the interactions between the drugs and the eukaryotic ribosome, we propose a unifying hypothesis for read-through enhancement by small molecules, highlighting the role of decoding center rearrangements and intersubunit rotation dynamics.
PubMed: 40273100
DOI: 10.1073/pnas.2420261122
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.35 Å)
Structure validation

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