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Scientists determine the structure of human Monoamine Oxidase B (MAO B)

Scientists from Emory University School of Medicine and the University of Pavia, Italy, have determined for the first time the three-dimensional structure of monoamine oxidase B (MAO B) an enzyme important in several major disease processes; particularly age-related neurological disorders. Understanding the detailed structure of the enzyme should provide a framework for designing new neuroprotective drugs. The research will be published in the January 2002 print edition of Nature Structural Biology and in the online edition on Nov. 26, 2001.

Monoamine oxidases (MAO B and MAO A) are well-known targets for antidepressant drugs and for drugs used to treat neurological disorders and diseases of aging, such as Parkinsons disease and Alzheimers disease. MAO A and MAO B are attached to the outer membrane of the mitochondria the energy powerhouses of cells and function to oxidize amine neurotransmitters such as dopamine and serotonin. Through their model of the enzymes structure, the Emory and Pavia scientists revealed the architecture of the enzymes active site, which is responsible for its catalytic properties. They also described sites on the enzyme responsible for its binding to the membrane.

Pharmacologists have designed a number of drugs, both reversible and irreversible, that inhibit MAO B and are used to treat neurological disorders. For example, the MAO B inhibitor deprenyl is administered to increase the effectiveness of L-dopa therapy in the treatment of Parkinsons disease and to provide neuroprotective effects in patients with pre-Parkinsons syndrome. Recent studies have also demonstrated that MAO B is inhibited by compounds present in tobacco smoke, which may contribute to the addictive properties of tobacco use. Scientific and clinical interest in these enzymes has been ongoing for more that 40 years and has resulted in more than 15,000 papers published on their biological properties.

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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
25-Nov-2001


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