In an effort to better understand a certain disease-causing enzyme, British researchers have created a "map" of more than 100 proteins this enzyme is known to affect. They then identified a druglike molecule that blocks this enzyme to preserve these essential proteins.
The research could aid in the development of new drugs for cancer and inflammatory diseases.
The enzyme in question, known as N-myristoyltransferase (NMT), causes irreversible damage to proteins and has been linked to a range of diseases including cancer, epilepsy and Alzheimer's disease.
Using living human cancer cells, investigators at Imperial College London identified more than 100 proteins that NMT modifies. Over several years, the team used mass spectrometry to get a complete picture of how an NMT inhibitor molecule affects all the proteins under the control of NMT.
Previously, scientists knew of only a handful of proteins that NMT modified during apoptosis--the process of programmed cell death. But the new study results identified other proteins affected by NMT. Chemotherapy activates apoptosis to kill cancer cells, but in drug-resistant cancer, this process of apoptosis gets deactivated. So the newly discovered proteins suggest a different strategy to combat drug resistance in cancer treatment.
"This 'global map' allows us to understand what the effects of inhibiting NMT will be. This means we can determine which diseases it might be possible to combat by targeting NMT, enabling us as a next step to explore how effective such treatments could be," lead researcher Ed Tate, a professor in the department of chemistry at Imperial College London, said in a statement.
Using the map, Tate and his colleagues identified a small, druglike molecule that can block the activity of NMT and inhibit its ability to change these key proteins.
- get more from Imperial College London
- see the study abstract