A team of researchers led by Prof. Dr. Carola Hunte has succeeded in describing how the antimalarial drug atovaquone binds to its target protein.
The scientists used x-ray crystallography to determine the three-dimensional structure of the protein with the active substance bound.
The drug combination atovaquone-proguanil (Malarone) is a medication used worldwide for the prevention and treatment of malaria.
Hunte and her team conducted the research at the Institute for Biochemistry and Molecular Biology of the Faculty of Medicine and the Centre for Biological Signalling Studies BIOSS at the University of Freiburg.
Malaria is one of the most dangerous tropical diseases in the world. Anopheles mosquitoes infected with Plasmodium species - unicellular parasites - transmit the disease by biting. Atovaquone blocks a protein of the respiratory chain in the mitochondria, the power plants of the cell, thus killing off the parasites.
However, the pathogen is susceptible to mutations so that drug resistant strains are arising and spreading.
The Freiburg scientists have now paved the way for the development of improved drugs by revealing the precise binding mode of atovaquone to the target protein.
They used the mitochondrial protein from cells of baker's yeast for their analyses due to its close resemblance to the parasitic protein.
The findings are published in the journal Nature Communications.