Structure of the MMP8 protein. Based on PyMOL rendering of PDB 1a85 Credit: Emw
Researchers identify a potentially significant new application for a well-known human enzyme that may help treat respiratory diseases eg asthma. Many enzymes are already well characterised and their functions fairly well understood eg. MMP8 is present in connective tissues of most mammals, where it breaks the chemical bonds found in collagen. In pre-clinical research Dr F Hollfelder (Dept of Biochemistry at Cambridge) and Dr L. Jermutus, Sr Director (R&D at MedImmune) mapped a list of 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. Of particular interest was how MMP8 was able to disable IL-13, which is known to play an important role in several inflammatory diseases such as asthma and dermatitis. The researchers believe this may be a previously-unknown way in which the body regulates the action of IL-13, preventing these diseases in the majority of individuals. If so, it could provide an interesting target for new drugs against these common diseases.
Designing new enzymes has proven an extremely difficult technical challenge, hence the drive to find new uses for previously ‘understood’ enzymes. By focusing on human proteases, rather than bacterial proteases – which are actually easier to source – the researchers are confident that their research will be far more applicable to drug discovery.
“Our approach is new: we ‘recycle’ known enzymes and ask whether they can do other things than the ones they are known for,” adds Dr Jermutus. “In fact, we believe we have found other enzymes that could be similarly deployed against other disease-causing proteins, and this approach, if expanded, could provide further leads for new drugs.” Dr Hollfelder adds: “Without MedImmune, our work would have stopped after seeing and characterising the interactions. The additional extension to cell and mouse models would have been inconceivable in my basic science group.”
http://www.cambridgenetwork.co.uk/news/moonlighting-molecules-new-uses-for-old-enzymes/
Recent Comments