title: Rational Design of Proteasome Inhibitors as Antimalarial Drugs.
abstract: One life, two strategies: Crucial structural differences between the human and the Plasmodium falciparum proteasomes were recently identified. A combination of cryo-EM and functional characterization enabled the design of a selective antimalarial proteasome inhibitor that shows low toxicity in the host. When used with artemisinin, this ligand offers a new approach for the efficient treatment of malaria at all stages of the parasite lifecycle.
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748, Garching, Germany. camille.le-chapelain@tum.de.
authors.forename: Camille
authors.identifier: 0000-0001-5347-6035
authors.initials: C
authors.lastname: Le Chapelain
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM), Department Chemie, Technische Universität München, Lichtenbergstrasse 4, 85748, Garching, Germany. michael.groll@tum.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D008958:Models, Molecular; D008968:Molecular Conformation; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D061988:Proteasome Inhibitors
keywords: cryo-electron microscopy; drug design; malaria; proteasome; structure-activity relationship