Featured Research

from universities, journals, and other organizations

Scientists discover 'Achilles' heel' of clot-buster

Date:
March 8, 2012
Source:
Cell Press
Summary:
A new study provides remarkable new insight into how plasmin is produced. This work may lead to more effective clot-busting drugs.

Everyone is familiar with the pain of skinned knees. However, the complex pathway of proteins that works behind the scenes after the bleeding has stopped is not as well known. Central to this process is the production of plasmin, a powerful blood enzyme that disposes of blot clots. Doctors also harness the "clot busting" abilities of plasmin to treat patients who suffer heart attack or stroke. Now, a study published by Cell Press on March 8th in the journal Cell Reports provides remarkable new insight into how plasmin is produced. This work may lead to more effective clot-busting drugs.

Plasmin is released into the blood in an inactive form called plasminogen. Circulating plasminogen is curled up in a "closed," activation-resistant form. In order for plasminogen to be converted to plasmin, it must first undergo a dramatic change in shape and "open" itself up. "We know that activation of plasminogen is tightly regulated," explains senior study author, Prof. James Whisstock, from Monash University in Melbourne, Australia. "However, without knowing the atomic details of the closed form of plasminogen, it is impossible to understand what causes it to change shape and how it is converted to plasmin by plasminogen activators."

Researchers from Monash University and the Australian Synchrotron have now solved the long-sought-after atomic structure of closed plasminogen. "We were very surprised to find that a simple sugar tethered to plasminogen guards access to the site of activation," says Dr. Tom Caradoc-Davies, from the Australian Synchrotron. Most remarkably, however, the researchers also found that plasminogen plays a kind of peek-a-boo with the blood clot. "We found one part of plasminogen seems to be very unstable and transiently opens up a tiny bit. Proteins in the blood clot bind to this 'Achilles' heel' when it is exposed, trapping plasminogen in the open form that can be activated," says lead author, Dr. Ruby Law, from Monash University.

"We use plasminogen-activating drugs to treat stroke and other life-threatening disorders associated with blood clots. However, until now, the molecular details for these therapeutic effects have never been understood," concludes co-senior author, Paul Coughlin, a clinical hematologist from the Australian Centre for Blood diseases. "Now, with the structure of plasminogen and an enhanced understanding of how it is converted to plasmin, we finally have a platform to develop new and more effective clot-busting therapeutics."


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ruby H.P. Law, Tom Caradoc-Davies, Nathan Cowieson, Anita J. Horvath, Adam J. Quek, Joanna Amarante Encarnacao, David Steer, Angus Cowan, Qingwei Zhang, Bernadine G.C. Lu et al. The X-ray Crystal Structure of Full-Length Human Plasminogen. Cell Reports, 08 March 2012 DOI: 10.1016/j.celrep.2012.02.012

Cite This Page:

Cell Press. "Scientists discover 'Achilles' heel' of clot-buster." ScienceDaily. ScienceDaily, 8 March 2012. <www.sciencedaily.com/releases/2012/03/120308132758.htm>.
Cell Press. (2012, March 8). Scientists discover 'Achilles' heel' of clot-buster. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2012/03/120308132758.htm
Cell Press. "Scientists discover 'Achilles' heel' of clot-buster." ScienceDaily. www.sciencedaily.com/releases/2012/03/120308132758.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins