Humans coordinate their movement and behavior through chemical signalling systems. The most advanced of these is the central nervous system (CNS) which utilizes a spectrum of biogenic amines, such as serotonin, noradrenaline, and dopamine, as specific neurotransmitters. Neurotransmitter level in the brain high highly regulated, mainly through three routes: by their synthesis, transport and ultimately, degradation. Monoamine oxidases (MAOs) are the key enzymes in the human brain that provide the catabolic regulation of the signaling amines. MAOs hold a powerful attraction for biochemists, pharmacologists and neurologists. Conventional treatment of numerous human neurological disorders such as mental depression, parkinsonism, and Alzheimer's disease is based on using specific inhibitors of MAOs. Little is known, though, about the molecular mechanism of catalysis by MAOs, or the structural determinants definition the substrate and the inhibitor specificity of these enzymes. The goal of this proposal is to create a structural basis for understanding of the molecular mechanism of monoamine oxidases; to define the structural determinants of the substrate and inhibitor specificity of human MAO and B types using MAON, a homolog that is closely related to human MAO A and B.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS037495-04
Application #
6490932
Study Section
Biochemistry Study Section (BIO)
Program Officer
Oliver, Eugene J
Project Start
1999-01-05
Project End
2003-12-31
Budget Start
2002-01-01
Budget End
2003-12-31
Support Year
4
Fiscal Year
2002
Total Cost
$238,698
Indirect Cost
Name
University of California San Francisco
Department
Biochemistry
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143