Researchers from Imperial College London have gained new knowledge into how a disease-causing enzyme makes changes to proteins and how to stop it.
The enzyme is known as N-myristoyltransferase (NMT) and researchers are hopeful that their new discovery may lead to the development of new treatments for cancer and other inflammatory conditions. In the study, researchers found that the human body produces a molecule that is capable of blocking NMT's activities. They have also identified specific protein substrates where this molecule has a potent impact. For the study, researchers used living human cancer cells to identify more than 100 proteins that NMT modifies, with almost all these proteins being identified for the very first time in their natural environment.
"We now have a much fuller picture of how NMT operates, and more importantly how it can be inhibited, than ever before. This is the first time that we have been able to look in molecular detail at how this potential drug target works within an entire living cancer cell, so this is a really exciting step forward for us," Lead researcher Professor Ed Tate, from the Department of Chemistry at Imperial College London said in a press statement. "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."
The study authors started the project by conducting a detailed large scale study exploring proteins under the control of NMT, but the scientists still needed information on the function of these proteins and how they are modified. Using mass spectrometry, they were able to quantify the effect of a NMT inhibitor molecule. A process known as apoptosis, which programmes a cell to die - for example because its DNA has been damaged helped researchers examine the interaction between the molecule and the enzyme.
"On the back of these results we are looking to test a drug that will have the most potent impact on blocking NMT's ability to modify proteins, and we have started working with collaborators at the Institute of Cancer Research and elsewhere on some very promising therapeutic areas. We are still at an early stage in our research but we have already identified several very potent drug-like NMT inhibitors that are active in animal disease models, and we hope to move towards clinical trials over the next five to ten years," the researchers continued.
The study findings were published online in the journal Nature Communications. The project was funded by Cancer Research UK and The Biotechnology & Biological Sciences Research Council, with further support from The Medical Research Council, The Engineering and Physical Sciences Research Council, and the European Union.
