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Enzymes could be new target for anti-malarial drugs

27 May 2019, 03:18 ( 2 Months ago)

DF Report
"Our new inhibitor, ATC, named after the pop group ‘A Touch of Class’. Just 46 atoms by the exit channel can gum up a protein of more than 10000 atoms." Press Release Photo : ADRIAN GOLDMANIN TUTKIMUSRYHMÄ/University of Helsinki.

A recent study of enzyme inhibitors revealed potential new routes to anti-malarial drugs, said a press release of University of Helsinki.

The study, carried out in collaboration by the researchers at the University of Leeds and University of Helsinki, looked at enzymes that are important in plants in cold, drought and salt stress.

These enzymes are also important in the life cycle of protozoan parasites – such as the ones that cause Malaria, African sleeping sickness and Toxoplasma – the reason that pregnant woman shouldn’t touch cats. Toxoplasma infects about 30% of the world’s population, including up to 90% in some European countries, and has been connected to schizophrenia and other mental illnesses.

Malaria, on the other hand, infects about 250 million people in developing countries, causing about 500,000 deaths each year. Global warming will lead to the malaria mosquito vector re-emerging as far North as England by 2050 – and resistance to the front-line drug, artemisinin, is emerging.

The new inhibitors do not work against protozoan parasites yet, but these scientists did discover compounds that could be potential inhibitors to help fight against diseases.

Adrian Goldman, the senior author on the study, remarked “It just shows how important serendipity is. We designed our inhibitor, ATC, to do one thing - but it does something completely different and much more interesting.”

While it is known that other enzymes in this family pump both protons and sodium ions, it has always been unclear how. However, thanks to this research the researchers think they now understand.

A “push-me-pull-you” mechanism explains all.  The pull side would pump a proton, so that the push side can pump a sodium, and so on.

Professor Adrian Goldman from the School of Biomedical Sciences at the University of Leeds led the research in collaboration with Professor Jari Yli-Kauhaluoma, Dr. Henri Xhaard and Professor Seppo Meri at the University of Helsinki.