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.
Organizational Affiliation:
Department of Integrated Structural Biology, Institute of Genetics and Molecular and Cellular Biology, University of Strasbourg, Illkirch, France.
Laboratory of Structural Biology, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands.
Department of Biology, Texas A&M University, College Station, TX, USA.
Federal Research Center "Kazan Scientific Center of Russian Academy of Sciences", Kazan, Russia.
Moscow Institute of Physics and Technology, Dolgoprudny, Russia.
The Joint Institute for Nuclear Research, Dubna, Russia.
Download Mendeley
