Researchers at Monash University have used x-ray beams created by the Australian Synchrotron (AS) to discover how enzymes work to dissolve blood clots and clean up damaged tissue in the body - a finding that could ultimately lead to a reduction in the number of heart disease-related deaths occurring each year as a result of blood clots.

Dr Tom Caradoc-Davies, Principal Scientist on the macromolecular crystallography beamline said the results came after months of collaboration between Monash University researchers, led by Professor James Whisstock, and the AS science group.

“We strongly believe these findings will lead to the design of better anti-blood clotting drugs and drugs to actively treat bleeding disorders and certain cancers,” said Dr Caradoc-Davies.

The Australian Synchrotron provides highly specialised research capabilities, unique within the Southern hemisphere. Using the facility‟s micro-crystallography and small and wide angle x-ray scattering (SAXS/WAXS) research stations, Australian scientists were able to identify the structure of a blood protein called plasminogen, a precursor of the enzyme plasmin, which assists in dissolving blood clots and is also implicated in some cancers.

Dr Caradoc-Davies said the Monash researchers and the AS science team had raced against the clock to be first in the world to publish the findings in the science journal Cell Reports. The paper titled “The X-ray crystal structure of full length Human Plasminogen” was published in Cell Reports today (9 March 2012).

“We knew that other research groups, some representing major pharmaceutical interests, were working on the same problem and our competitive advantage lay in being able to use the Australian Synchrotron to 'identify' the crystal structure of plasminogen,” said Dr Caradoc-Davies.

“Because we could look at the atomic nature of plasminogen using the synchrotron, we were able to answer an almost century old scientific question – how is plasminogen really activated in the body.”

Professor James Whisstock, from the School of Biochemistry and Molecular Biology, who led the Monash University-driven study, said the findings illustrated just how important the Australian Synchrotron was to modern science and Australia‟s ability to compete at an international level.

“In the past, the molecular details of plasminogen-activating drugs used to treat strokes were not entirely understood. This latest discovery by Monash and the AS science team means drug companies will now be able to fine tune their development of next generation anti clotting/ 'clot busting' drugs and cancer treatments,” said Professor Whisstock.

Historically, clinicians had used drugs to convert plasminogen into plasmin to treat patents in the hours immediately after heart attack or stroke. Plasmin inhibitors had also been used as anti-cancer therapeutics. The true nature of how these drugs affected plasminogen however was not known until the results of this study were finalised.

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