Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Toward a Better Drug against Malaria


Freiburg structural biologists explain on the molecular level, how the drug atovaquone acts on the pathogen of the disease

A research team 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.

Molecule in a pocket: The illustration shows how atovaquone binds to its target protein. Graphic: Dominic Birth, Carola Hunte

The drug combination atovaquone-proguanil (Malarone®) is a medication used worldwide for the prevention and treatment of malaria. The data and the resulting findings concerning the mode of action of atovaquone could lead to improved medications against the tropical disease.

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. The scientists published their findings in the journal Nature Communications.

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 target protein of atovaquone is the third of four enzymes of the respiratory chain in the mitochondrion. The amino acid chains of the protein form a three-dimensional pocket. The molecule of the active substance fits perfectly into this pocket, binding to amino acids at numerous positions.

These interactions are crucial for the effect atovaquone has in Plasmodium cells, ultimately leading to the death of the pathogen. The researchers conducted a protein sequence analysis, revealing that most of these docking sites are identical in the pathogen, baker’s yeast and in human cells. Atovaquone forms several bonds that are specific to the Plasmodium protein in the open area of the binding pocket.

In addition, the structural analysis revealed the molecular basis of resistances: Due to mutations that change the structure of the target protein, the substance cannot reach the designated binding mode – it doesn’t fit perfectly into the pocket anymore.

The data provides an important basis for improving antimalarial drugs. Scientists could now modify the molecular structure of atovaquone by means of structure-based drug design, ensuring that the active substance forms necessary bonds – and that the pathogen is no longer resistant to it.

Prof. Dr. Carola Hunte | University of Freiburg
Further information:

Further reports about: Biochemistry Biology Drug Malaria Molecular Plasmodium antimalarial drugs mutations parasites resistant structure tropical

More articles from Life Sciences:

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

nachricht Researchers Discover New Anti-Cancer Protein
22.03.2018 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Modular safety concept increases flexibility in plant conversion

22.03.2018 | Trade Fair News

New interactive map shows climate change everywhere in world

22.03.2018 | Earth Sciences

New technologies and computing power to help strengthen population data

22.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>