Abstract

Molybdenum is an essential element in enzymes involved in purine metabolism, sulfur metabolism, and the assimilation of inorganic nitrogen. Exposure to excess molybdenum has been linked with gout and atherosclerosis. Molybdenum levels in the soil affect the levels of nitrate and nitrite and interfere with normal copper metabolism. Current evidence indicates that molybdoenzymes fall into two classes. This research is related to the class of molybdoenzymes which includes the xanthine oxidases, the sulfite oxidases and the nitrate reductases. These enzymes contain a common molybdenum cofactor which is thought to be a monomeric molybdenum center with ligating sulfur atoms. The objectives of this research are to investigate structural models for the molybdenum centers of these enzymes by an integrated program of synthesis and chemical, spectroscopic and x-ray structural studies on well-defined molybdenum compounds. Special emphasis will be given to monomeric molybdenum(V) compounds, compounds which contain sulfido or hydrosulfido groups attached to molybdenum, and compounds in which the coordination environment about the metal is controlled by sterically constraining ligands. Compounds will be characterized by electron paramagnetic spectroscopy (EPR), 95Mo nuclear magnetic resonance spectroscopy (NMR), and x-ray crystallography.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037773-13
Application #
3293466
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1986-06-01
Project End
1991-05-31
Budget Start
1987-06-01
Budget End
1988-05-31
Support Year
13
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Arizona
Department
Type
Schools of Arts and Sciences
DUNS #
City
Tucson
State
AZ
Country
United States
Zip Code
85722

  Publications

Kappler, Ulrike; Enemark, John H (2015) Sulfite-oxidizing enzymes. J Biol Inorg Chem 20:253-64
Davis, Amanda C; Johnson-Winters, Kayunta; Arnold, Anna R et al. (2014) Kinetic results for mutations of conserved residues H304 and R309 of human sulfite oxidase point to mechanistic complexities. Metallomics 6:1664-70
Klein, Eric L; Belaidi, Abdel Ali; Raitsimring, Arnold M et al. (2014) Pulsed electron paramagnetic resonance spectroscopy of (33)S-labeled molybdenum cofactor in catalytically active bioengineered sulfite oxidase. Inorg Chem 53:961-71
Johnson-Winters, Kayunta; Davis, Amanda C; Arnold, Anna R et al. (2013) Probing the role of a conserved salt bridge in the intramolecular electron transfer kinetics of human sulfite oxidase. J Biol Inorg Chem 18:645-53
Klein, Eric L; Astashkin, Andrei V; Raitsimring, Arnold M et al. (2013) Applications of pulsed EPR spectroscopy to structural studies of sulfite oxidizing enzymes(). Coord Chem Rev 257:110-118
Davis, Amanda C; Cornelison, Matthew J; Meyers, Kimberly T et al. (2013) Effects of mutating aromatic surface residues of the heme domain of human sulfite oxidase on its heme midpoint potential, intramolecular electron transfer, and steady-state kinetics. Dalton Trans 42:3043-9
Klein, Eric L; Raitsimring, Arnold M; Astashkin, Andrei V et al. (2012) Identity of the exchangeable sulfur-containing ligand at the Mo(V) center of R160Q human sulfite oxidase. Inorg Chem 51:1408-18
Astashkin, Andrei V; Rajapakshe, Asha; Cornelison, Matthew J et al. (2012) Determination of the distance between the Mo(V) and Fe(III) heme centers of wild type human sulfite oxidase by pulsed EPR spectroscopy. J Phys Chem B 116:1942-50
Rajapakshe, Asha; Meyers, Kimberly T; Berry, Robert E et al. (2012) Intramolecular electron transfer in sulfite-oxidizing enzymes: probing the role of aromatic amino acids. J Biol Inorg Chem 17:345-52
Rajapakshe, Asha; Tollin, Gordon; Enemark, John H (2012) Kinetic and thermodynamic effects of mutations of human sulfite oxidase. Chem Biodivers 9:1621-34

Showing the most recent 10 out of 73 publications