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

Science advances 2022 May 27

filter terms:

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 80S 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.

Citation

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. E-site drug specificity of the human pathogen Candida albicans ribosome. Science advances. 2022 May 27;8(21):eabn1062