Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Mechanism of read-through enhancement by aminoglycosides and mefloquine.
Journal, issue, pages	Proc Natl Acad Sci U S A, Vol. 122, Issue 17, Page e2420261122, Year 2025
Publish date	Apr 29, 2025
Authors	Olga Kolosova / Yury Zgadzay / Artem Stetsenko / Anastasia P Sukhinina / Anastasia Atamas / Shamil Validov / Andrey Rogachev / Konstantin Usachev / Lasse Jenner / Sergey E Dmitriev / Gulnara Yusupova / Albert Guskov / Marat Yusupov /
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 ...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.
External links	Proc Natl Acad Sci U S A / PubMed:40273100 / PubMed Central
Methods	EM (single particle)
Resolution	2.15 - 3.1 Å
Structure data	EMDB-16920: 40S body focused map of Candida albicans 80S ribosome in complex with mefloquine Method: EM (single particle) / Resolution: 3.1 Å EMDB-16921: 40S head focused map of Candida albicans 80S ribosome in complex with mefloquine Method: EM (single particle) / Resolution: 3.1 Å EMDB-16922: Combined map of Candida albicans 80S ribosome in complex with mefloquine Method: EM (single particle) / Resolution: 3.1 Å 50957 9g1z EMDB-50957: Cryo-EM map of Candida albicans 80S ribosome in complex with mefloquine (non-rotated state) PDB-9g1z: Structure of Candida albicans 80S ribosome in complex with mefloquine (non-rotated state) Method: EM (single particle) / Resolution: 3.1 Å 50990 9g30 EMDB-50990: Cryo-EM map of the Candida albicans ribosome with tRNA-fMet, mRNA, and compounds (GEN and MFQ) shows strong density for the A site tRNA PDB-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 Method: EM (single particle) / Resolution: 2.35 Å 51103 9g6j EMDB-51103: Cryo-EM map of the Candida albicans ribosome with tRNA-fMet, mRNA, and compounds (GEN and MFQ) with strong density for the P-site tRNA PDB-9g6j: The structure of the Candida albicans ribosome with tRNA-fMet, mRNA, and compounds (GEN and MFQ) with strong density for the P-site tRNA Method: EM (single particle) / Resolution: 2.15 Å
Chemicals	ChemComp-ZN: Unknown entry ChemComp-YMZ: Mefloquine ChemComp-SPK: SPERMINE (FULLY PROTONATED FORM) ChemComp-GET: GENETICIN / antibiotic*YM
Source	candida albicans (yeast) candida albicans sc5314 (yeast) escherichia coli (E. coli)
Keywords	RIBOSOME / Candida Albicans / Readthrough / Mefloquine / mRNA / geneticin G418