The structures of three extradiol dioxygenases involved in the microbial degradation of detrimental aromatic compounds will be determined at atomic resolution by X-ray crystallography. Structures of complexes of the enzymes with substrates and inhibitors also will be determined. The structural information will be analyzed with respect to the biochemical functions of these and related enzymes. The immediate goals of this project include the specification of the structural determinants of substrate binding and catalysis. Extradiol dioxygenases are a class of nonheme,Fe(II)-dependent enzymes that play critical roles in the catabolism of aromatic compounds by virtue of their ability to catalyze the cleavage of aromatic rings. Pathways for the synthesis and degradation of several key metabolites, including amino acids, nucleic acids, vitamins, and hormones, require dioxygenase-catalyzed ring cleavage reactions. Extradiol dioxygenases also are intimately involved in the microbial degradation of many natural and synthetic aromatic compounds. The targeted enzymes catalyze the cleavage of aromatic rings in microbial pathways that degrade biphenyl, dibenzo-p-dioxin, dibenzofuran and their chlorinated analogs. This group of substrates includes a number of significant health risks. This project is part of a collaborative effort whose goals include elucidation of the mechanism of ring cleavage by extradiol dioxygenases, elucidation of the mechanism of irreversible inhibition of these enzymes by chlorinated metabolites, and development of microbial systems with an increased ability to degrade a broad range of detrimental aromatic and chloroaromatic pollutants.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM052381-01
Application #
2191376
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1995-05-08
Project End
1998-04-30
Budget Start
1995-05-08
Budget End
1996-04-30
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Purdue University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907