The long term objectives of the proposed research are: 1) To advance our understanding of the mechanisms for electron transfer in oxidation-reduction reactions catalyzed by flavoenzymes; 2) To evaluate the role of the coenzyme in those flavoproteins where catalysis does not involve a net oxidation-reduction reaction. Studies related to the latter objective will seek to determine the structure of a second chromophore in E. coli DNA photolyase, an enzyme which also contains a blue FAD radical, and to evaluate the role of both chromophores in catalysis. Studies on the mechanism of yeast DNA photolyase will seek to determine the function and the structure of a reduced flavin prosthetic group and of a possible second chromophore. Analogous studies with photolyase from bovine leucocytes and a human promyelocytic cell line will help in defining the diversity in chromophore content and mechansim with enzymes from different sources. Studies with sarcosine oxidase from Corynebacteria will focus on the catalytic functions and properties of its two nonequivalent flavins and will also include experiments to evaluate the possible role of tetrahydrofolate in catalysis. Additional studies will seek to determine whether other flavoproteins from Corynebacteria contain both covalent and noncovalent flavin, similar to sarcosine oxidase. Studies with lactate oxidase will seek to identify an active site base that abstracts the Alpha-proton during lactate oxidation. Evidence regarding the role and origin of a stable flavin radical will be investigated in studies with methanol oxidase which will also seek to characterize the mechanism of methanol oxidation and the nature of a red complex formed with the enzyme and azide. The proposed research will involve kinetic and structural analysis and will include reactions with normal substrates, substrate analogues, inhibitors and modified flavins. The structure of the chromophore(s) in human DNA photolyase could be of therapeutic significance in treating certain forms of xeroderma pigmentosum.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Physical Biochemistry Study Section (PB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Hahnemann University
Schools of Medicine
United States
Zip Code
Kommoju, Phaneeswara-Rao; Chen, Zhi-wei; Bruckner, Robert C et al. (2011) Probing oxygen activation sites in two flavoprotein oxidases using chloride as an oxygen surrogate. Biochemistry 50:5521-34
Bruckner, Robert C; Winans, Jennifer; Jorns, Marilyn Schuman (2011) Pleiotropic impact of a single lysine mutation on biosynthesis of and catalysis by N-methyltryptophan oxidase. Biochemistry 50:4949-62
Jorns, Marilyn Schuman; Chen, Zhi-Wei; Mathews, F Scott (2010) Structural characterization of mutations at the oxygen activation site in monomeric sarcosine oxidase . Biochemistry 49:3631-9
Zhao, Guohua; Bruckner, Robert C; Jorns, Marilyn Schuman (2008) Identification of the oxygen activation site in monomeric sarcosine oxidase: role of Lys265 in catalysis. Biochemistry 47:9124-35
Hassan-Abdallah, Alshaimaa; Zhao, Guohua; Chen, Zhi-wei et al. (2008) Arginine 49 is a bifunctional residue important in catalysis and biosynthesis of monomeric sarcosine oxidase: a context-sensitive model for the electrostatic impact of arginine to lysine mutations. Biochemistry 47:2913-22
Hassan-Abdallah, Alshaimaa; Zhao, Guohua; Jorns, Marilyn Schuman (2008) Covalent flavinylation of monomeric sarcosine oxidase: identification of a residue essential for holoenzyme biosynthesis. Biochemistry 47:1136-43
Zhao, Gouhua; Jorns, Marilyn Schuman (2006) Spectral and kinetic characterization of the michaelis charge transfer complex in monomeric sarcosine oxidase. Biochemistry 45:5985-92
Chen, Zhi-wei; Hassan-Abdulah, Alshaimaa; Zhao, Gouhua et al. (2006) Heterotetrameric sarcosine oxidase: structure of a diflavin metalloenzyme at 1.85 A resolution. J Mol Biol 360:1000-18
Hassan-Abdallah, Alshaimaa; Zhao, Guohua; Jorns, Marilyn Schuman (2006) Role of the covalent flavin linkage in monomeric sarcosine oxidase. Biochemistry 45:9454-62
Hynson, Robert M G; Mathews, F Scott; Schuman Jorns, Marilyn (2006) Identification of a stable flavin-thiolate adduct in heterotetrameric sarcosine oxidase. J Mol Biol 362:656-63

Showing the most recent 10 out of 61 publications