E-site drug specificity of the human pathogen Candida albicans ribosome - Archive ouverte HAL Access content directly
Journal Articles Science Advances Year : 2022

E-site drug specificity of the human pathogen Candida albicans ribosome

Artem Stetsenko
Cheng Wu
Matthew Sachs

Abstract

Candida albicans 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 C. albicans 80 S 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 C. albicans and forms a basis for further antifungal drug development.
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Dates and versions

hal-03813407 , version 1 (13-10-2022)

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Yury Zgadzay, Olga Kolosova, Artem Stetsenko, Cheng Wu, David Bruchlen, et al.. E-site drug specificity of the human pathogen Candida albicans ribosome. Science Advances , 2022, 8 (21), pp.eabn1062. ⟨10.1126/sciadv.abn1062⟩. ⟨hal-03813407⟩
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