Copper amine oxidases (CAO) are ubiquitously found in Nature and catalyze the oxidative deamination of primary amines in prokaryotes and eukaryotes. By virtue of the correlation between increased CAO activities and certain chronic diseases in man, much attention has been drawn to the field and has led to a number of exciting findings over the past decade. Perhaps, most important was the identification of trihydroxyphenylalanine quinone (TPQ) as the redox cofactor in CAO. Surprisingly, the covalent cofactor was found to be derived from the autocatalytic modification of an active site tyrosine by a post- translational event requiring molecular oxygen and a cupric ion. Over the years a wealth of knowledge apropos of the mechanism for the utilization of the quinocofactor during catalysis has accumulated and led to a well established model for the conversion of amines to their corresponding aldehydes. Nonetheless, a full understanding of the strategies employed by CAO to catalyze the transformation of the precursor tyrosine to the active mature cofactor is lacking. In an effort to address fundamental questions regarding roles of the active site copper and the contributions of protein-protein interactions in this process, the specific aims of proposed research are (1) to evaluate and identify a potential chemical intermediate (2) to assess the role of the electrophilicity of copper and (3) to ascertain the role of intersubunit communication in the mechanism for the biogenesis of TPQ.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM064215-01
Application #
6406408
Study Section
Physical Biochemistry Study Section (PB)
Program Officer
Marino, Pamela
Project Start
2001-11-16
Project End
Budget Start
2001-11-16
Budget End
2002-11-15
Support Year
1
Fiscal Year
2001
Total Cost
$34,832
Indirect Cost
Name
University of California Berkeley
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704