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Molecule May Help Boost "Good Cholesterol"

Date:
December 28, 1997
Source:
Southern Research Institute
Summary:
For the first time ever, cardiovascular disease researchers can now get a good look at human apolipoprotein A-I (apo A-I) — the major protein component of high density lipoprotein (HDL). Scientists caution that while these results may not immediately lead to a new medication to control cholesterol, another very important piece in the puzzle has been revealed in the fight against heart disease.

Birmingham, Ala. — For the first time ever, cardiovascular disease researchers can now get a good look at human apolipoprotein A-I (apo A-I) — the major protein component of high density lipoprotein (HDL). HDL is known as the "good cholesterol" because it protects against heart disease, the country's leading cause of death. Scientists caution that while these results may not immediately lead to a new medication to control cholesterol, another very important piece in the puzzle has been revealed in the fight against heart disease.

"A lot of science is done ‘under the lamp post,' so to speak," says David W. Borhani, Ph.D., a chemist at Southern Research Institute in Birmingham and leader of the apo A-I crystallography project. "Our new apo A-I structure has made that light a whole lot brighter now — giving researchers a clear picture to focus on."

In a paper recently published in the Proceedings of the National Academy of Sciences USA, researchers at Southern Research Institute (SRI) and the University of Alabama at Birmingham (UAB) describe how they determined the three-dimensional structure of apo A-I using x-ray crystallography — a method widely used to study the structures of biological macromolecules at atomic resolution. X-ray crystallography is also being used increasingly in rational drug design.

The new apo A-I structure is the result of a collaboration between Southern Research's Borhani and UAB professors Jeffrey A. Engler, Ph.D. and Christie G. Brouillette, Ph.D., and their graduate student Danise P. Rodgers, Ph.D.

Scientists have studied lipoproteins — such as HDL — for decades hoping to advance cardiovascular disease research and drug development. Human clinical trials have shown that the higher the HDL level in a person's blood, the lower the risk of developing atherosclerosis and coronary artery disease. Understanding the structure of apo A-I is key to understanding this protective effect of HDL.

The Birmingham apo A-I model is important because it suggests what apo A-I looks like when bound to lipid in the HDL particle. As the researchers began to define this egg-shaped model, they realized its potential impact on the future of cardiovascular studies. "We began to call it our ‘Fabergι Egg'," said Engler, the team's molecular biologist, "because it was so rare and valuable."

Until now, scientists studying apo A-I have had to rely on educated guesses about the three-dimensional structure of this critical component of HDL. These guesses — or models — focused on two possible alternative structures: the "belt" model and the "picket fence" model.

The apo A-I structure determined by Borhani and colleagues strongly suggests that the "belt" model is correct and provides even more details about this model. "There are gaps in our understanding of how HDL works," said Borhani. "But studying this three-dimensional structure of apo A-I is an important step toward understanding the beneficial role HDL plays in preventing heart disease." — 30—


Story Source:

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


Cite This Page:

Southern Research Institute. "Molecule May Help Boost "Good Cholesterol"." ScienceDaily. ScienceDaily, 28 December 1997. <www.sciencedaily.com/releases/1997/12/971228233648.htm>.
Southern Research Institute. (1997, December 28). Molecule May Help Boost "Good Cholesterol". ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/1997/12/971228233648.htm
Southern Research Institute. "Molecule May Help Boost "Good Cholesterol"." ScienceDaily. www.sciencedaily.com/releases/1997/12/971228233648.htm (accessed September 20, 2014).

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