9G1Z
Structure of Candida albicans 80S ribosome in complex with mefloquine (non-rotated state)
This is a non-PDB format compatible entry.
Summary for 9G1Z
| Entry DOI | 10.2210/pdb9g1z/pdb |
| Related | 8CQ7 8CQW 8CRE 8OEQ |
| EMDB information | 50957 |
| Descriptor | 60S ribosomal protein L20, 18S rRNA, 40S ribosomal protein S0, ... (82 entities in total) |
| Functional Keywords | candida albicans, ribosome, readthrough, mefloquine |
| Biological source | Candida albicans SC5314 More |
| Total number of polymer chains | 79 |
| Total formula weight | 3115602.29 |
| Authors | Kolosova, O.,Zgadzay, Y.,Stetsenko, A.,Atamas, A.,Jenner, L.B.,Guskov, A.,Yusupov, M. (deposition date: 2024-07-10, release date: 2025-04-23, Last modification date: 2025-05-07) |
| Primary citation | Kolosova, 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: 40273100DOI: 10.1073/pnas.2420261122 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
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