Our blood has a built-in system for breaking up heart attack-inducing clots—and we’re a step closer to drugs that could switch that system on at will.

Australian researchers have won the decades-long race to define the structure of plasminogen—a protein whose active form quickly dissolves blood clots.

The current crop of clot-busting drugs have many side effects, including bleeding and thinning of the blood, so harnessing the body’s own mechanism for clearing clots could offer a better way.An Australian team led by Prof James Whisstock and Dr Ruby Law from Monash University, and Dr Tom Caradoc-Davies from the Australian Synchrotron, was able to manipulate the protein into a crystal that diffracts X-rays—allowing them to reveal the complex 3D structure.

“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,” Tom says.

In the past, the molecular details of plasminogen-activating drugs used to treat strokes were not entirely understood.

This latest discovery means that drug companies can fine-tune their development of next generation anti-clotting and “clot busting” drugs and cancer treatments—using their knowledge of the molecule’s structure to design drugs that “switch on” the protein.

This means finding a drug that would mimic the body’s own messengers by fitting into a special site on the protein.

“Once you know what the lock looks like, it’s much easier to make a key,” Tom says.

Photo: The molecular structure of plasminogen.

Credit: Prof James Whisstock/Australian Synchrotron

Australian Synchrotron, Tom Caradoc-Davies, Tom.Caradoc-Davies@synchrotron.org.au, www.synchrotron.org.au