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-Structure paper
Title | E-site drug specificity of the human pathogen ribosome. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 21, Page eabn1062, Year 2022 |
Publish date | May 27, 2022 |
Authors | Yury Zgadzay / Olga Kolosova / Artem Stetsenko / Cheng Wu / David Bruchlen / Konstantin Usachev / Shamil Validov / Lasse Jenner / Andrey Rogachev / Gulnara Yusupova / Matthew S Sachs / Albert Guskov / Marat Yusupov / |
PubMed Abstract | is a widespread commensal fungus with substantial pathogenic potential and steadily increasing resistance to current antifungal drugs. It is known to be resistant to cycloheximide (CHX) that binds ... is a widespread commensal fungus with substantial pathogenic potential and steadily increasing resistance to current antifungal drugs. It is known to be resistant to cycloheximide (CHX) that binds to the E-transfer RNA binding site of the ribosome. Because of lack of structural information, it is neither possible to understand the nature of the resistance nor to develop novel inhibitors. To overcome this issue, we determined the structure of the vacant 80 ribosome at 2.3 angstroms and its complexes with bound inhibitors at resolutions better than 2.9 angstroms using cryo-electron microscopy. Our structures reveal how a change in a conserved amino acid in ribosomal protein eL42 explains CHX resistance in and forms a basis for further antifungal drug development. |
External links | Sci Adv / PubMed:35613268 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.32 - 2.77 Å |
Structure data | EMDB-13737: Cryo-EM map of the vacant Candida albicans 80S ribosome EMDB-13741, PDB-7q08: EMDB-13744: Cryo-EM map of Candida albicans 80S ribosome in complex with phyllanthoside EMDB-13749: Cryo-EM map of the Candida albicans 80S ribosome in complex with anisomycin EMDB-13750: Cryo-EM map of the Candida albicans 80S ribosome in complex with blasticidin s |
Chemicals | ChemComp-SPD: ChemComp-PUT: ChemComp-MG: ChemComp-ZN: ChemComp-HOH: ChemComp-3HE: ChemComp-3K5: ChemComp-ANM: ChemComp-BLS: |
Source |
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Keywords | RIBOSOME / Candida albicans / cryo-EM / cycloheximide / drug design / phyllanthoside / anisomycin / peptidyl transferase center / blasticidin s |