Navigation Links
X-ray crystallography reveals structure of precursor to blood-clotting protein

ST. LOUIS Using state-of-the-art robotic and x-ray crystallographic equipment, researchers at Saint Louis University have revealed for the first time the molecular structure of the zymogen, or inactive, form of a blood-clotting enzyme.

In an article published in Proceedings of the National Academy of Sciences, Enrico Di Cera, M.D., chair of the department of biochemistry and molecular biology at Saint Louis University School of Medicine and lead researcher of the study, said the NIH-funded research offers important information about the protein.

"This research is very basic and very important," said Di Cera. "It provides a missing link between the inactive zymogen form of thrombin and the mature enzyme generated upon vascular injury."

Before thrombin becomes active, it circulates throughout the blood in the inactive zymogen form. When the active enzyme is needed, for example after a vascular injury, the coagulation cascade is initiated and the zymogen is converted into an active enzyme that causes blood to clot.

Blood clotting performs the important function of stopping blood loss after an injury. However, when triggered in the wrong conditions, clotting can lead to debilitating or fatal conditions like heart attack, stroke and deep vein thrombosis.

In previous laboratory research, Di Cera re-engineered thrombin to act as an anticoagulant, stopping blood from clotting and opening the door to the development of new therapeutic strategies for the treatment of thrombosis, the presence of blood clots in blood vessels, which is responsible for nearly a third of all deaths in the U.S.

While researchers have an understanding of the structure of active thrombin, very little was known about its zymogen form. In order to learn more, researchers used x-ray crystallography to gather data about the molecular structure of the protein.

The process involves growing a crystal of the protein, shooting x-ray beams through the crystal and analyzing the diffraction pattern generated on a detector plate in order to detail the three-dimensional structure of the protein.

The structure of the zymogen form of thrombin provides crucial details about the activation mechanism that sheds light on the way the mature enzyme works. Future research can capitalize on these new findings to define better strategies for therapeutic intervention.

"Until now, we've known nothing about the zymogen form of thrombin or any blood-clotting enzyme," said Di Cera. "All the structural information has been limited to the active form.

"We now know that the zymogen form of thrombin is very different from the mature enzyme, in ways that open new opportunities for therapeutic intervention."


Contact: Carrie Bebermeyer
Saint Louis University

Related biology news :

1. Scientists using X-ray vision to produce more nutritious flour
2. Researchers demonstrate nanoscale X-ray imaging of bacterial cells
3. E-beam and X-ray irradiation technologies
4. Lensless imaging of whole biological cells with soft X-rays
5. First X-ray lasers early success brings approval for next-phase facility
6. Early results from the worlds brightest X-ray source
7. LiXEdrom: Innovative measuring chamber for X-ray study of liquid jets
8. An X-ray for your genes
9. X-ray diffraction may play key role in stopping kissing bug, fungus
10. Study reveals homeowner perceptions in fire-prone areas
11. Study reveals specific gene in adolescent men with delinquent peers
Post Your Comments:
(Date:11/9/2015)...  Synaptics Inc. (NASDAQ: SYNA ), the leading ... into the automotive market with a comprehensive and dedicated ... consumer electronics human interface innovation. Synaptics, industry-leading touch controllers, ... automotive industry and will be implemented in numerous locations ... , Japan , and ...
(Date:11/2/2015)... , Nov. 2, 2015  SRI International has ... to provide preclinical development services to the National Cancer ... SRI will provide scientific expertise, modern testing and support ... of preclinical pharmacology and toxicology studies to evaluate potential ... --> The PREVENT Cancer Drug Development Program is ...
(Date:10/29/2015)... , Oct. 29, 2015  The J. Craig ... report titled, "DNA Synthesis and Biosecurity: Lessons Learned and ... Department of Health and Human Services guidance for synthetic ... 2010. --> --> ... also has the potential to pose unique biosecurity threats. ...
Breaking Biology News(10 mins):
(Date:11/30/2015)... Md. , Nov. 30, 2015 ... development company committed to the fostering and monetization ... the current and prospective initiatives designed to create ... Chief Executive Officer of Spherix. "Based on published ... future licensees exceeds $50 billion and Spherix will ...
(Date:11/30/2015)... , Nov. 30, 2015  Champions Oncology, Inc. (CSBR), ... services to personalize the development and use of oncology ... Executive Officer, will be presenting at the LD MICRO ... Pacific Standard Time (PST).  The conference, held at the ... Angeles, CA , will feature 200 small/micro-cap companies ...
(Date:11/30/2015)... 30, 2015 TapImmune, Inc. ... of innovative peptide and gene-based immunotherapeutics and vaccines for ... it will be presenting at the 8 th ... at 2.30 PM PT. Dr. John N. Bonfiglio ... be giving the presentation and will join TapImmune management ...
(Date:11/30/2015)... , Nov. 30, 2015  Aytu BioScience, Inc. (OTCQB: ... and related conditions, will present at two upcoming investor ... an interactive real-time virtual conference, to be held December ... Conference, to be held December 2 nd & ... and streamed live via webcast. ...
Breaking Biology Technology: