This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Monoamine oxidases ( A &B) are outer mitochondrial membrane-bound enzymes that play important roles in amine neurotransmitter metabolism. Sequence and modeling studies suggest human MAO A differs from all other mammalian MAO A in that it is monomeric rather than dimeric in the outer membrane due to a Glu151Lys mutation. Crystal structures of purified human and rat MAO A provide additional support for this hypothesis. To provide a direct experimental test, analogues of the inhibitor pargyline with a nitroxide spin label on the para position will be synthesized and covalently incorporated into the active sites of human and rat MAO A, the Lys151Glu mutant of human MAO A, and human MAO B. Structural data of the dimeric form of crystalline human MAO B show the distance between the active site cavities is 42 ?. This distance is readily determined by Double Quantum Coherence EPR measurements on these samples. The dipolar spectral data will provide distance information that will determine if these enzyme species are in their dimeric or monomeric forms in the mitochondrial outer membrane.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR016292-11
Application #
8363971
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2011-09-01
Project End
2012-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
11
Fiscal Year
2011
Total Cost
$482
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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