Promiscuous Proteins – Potential New Treatments?

ENZYMES catalyse almost every chemical reaction in biology, and the specificity and physiological roles of many have been well characterised over the years. However, a recent study has discovered that some enzymes may exhibit previously undescribed properties when studied in different settings. Recombinant enzymes are often administered as therapeutic agents, but the time and expense required to develop new agents are considerable. It is hoped that the current project, a collaboration between the University of Cambridge, MedImmune, and AstraZeneca, could identify a range of novel applications for previously characterised enzymes.

The research team investigated 27 human enzymes with known function by testing them against 24 potential protein drug targets. The results were unexpected, with a total of 23 previously unknown, specific enzyme activities being observed. One enzyme of particular interest was MMP-8, a metalloproteinase found in connective tissue and known for its ability to degrade collagen. Experiments in cell cultures and animal models revealed that MMP-8 may play a specific role in many inflammatory disorders through blockade of interleukin (IL)-13, a cytokine implicated in many inflammatory conditions, including asthma and dermatitis. This observation may reveal a novel mechanism through which IL-13 is regulated during homeostasis, which prevents the development of inflammatory processes. Dr Florian Hollfelder, University of Cambridge, Cambridge, UK, led the team of scientists and commented: “Because the enzyme already had a name and a function, nobody thought to see if it had a promiscuous side.”

The team intends to follow up on the other potential new drug target/enzyme interactions that they discovered with further experiments. There is also scope for a greater number of enzymes and protein targets to be investigated using the same experimental model, a resource which could lead to new treatments for a range of diseases.


Comments are closed.