Moonlighting molecules: finding new uses for old enzymes

A collaboration between the University of Cambridge and MedImmune, the global biologics research and development arm of AstraZeneca, has led researchers to identify a potentially significant new application for a well-known human enzyme, which may have implications for treating respiratory diseases such as asthma.

 “MMP8 is well-known to biochemists and we all thought we understood its function, but it’s clear that this – and probably many other enzymes – ‘moonlight’ and have several functions within the body.”

– Florian Hollfelder

Enzymes are biological catalysts – molecules that speed up chemical reactions within living materials. Many enzymes are already well characterised and their functions fairly well understood. For example, the enzyme known as MMP8 is present in the connective tissue of most mammals, where it breaks the chemical bonds found in collagen.

In pre-clinical research published in the journal Chemistry & Biology, Dr Florian Hollfelder from the Department of Biochemistry at Cambridge and Dr Lutz Jermutus, Senior Director, Research and Development at MedImmune, led a study to map a list of human enzymes (proteases) against potential protein drug targets.

Using automation technology at MedImmune, the team then tested each of the enzymes against each target protein in turn, allowing them to identify a significant number of so-far unknown interactions.


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