Dr. Marjorie A. Jones, Professor, Biochemistry
Department: Chemistry
Campus Phone: 438-2366
Research Area: Enzymes Involved in Heme Metabolism; Porphyrin as therapeutic Treatments
Porphyrins occur widely in nature serving a variety of biological functions. Porphyrin derivatives are involved in oxygen transport (hemoglobin), photosynthesis (chlorophylls), oxygen storage (myoglobin) as well as energy metabolism (cytochromes). Heme is a specific porphyrin that is the important non-protein component of hemoglobin. The general pathway for heme biosynthesis has been well known yet several of the enzymes are as yet poorly understood in terms of active site amino acids and catalytic mechanisms. In this lab, we study two of the enzymes involved in heme biosynthesis and are especially interested in the molecular recognition of substrate by the enzymes. Synthetic substrate analogs are used to probe the substrate fit into the active site of the two specific enzymes, Coproporphyrinogen Oxidase and Uroporphyrinogen Decarboxylase. Enzyme kinetics are used to assess substrate recognition. Thus enzyme activities are evaluated following solvent extractions and HP!
LC separations followed by spectroscopy. Covalent modification of active site amino acids is also an important method being used to evaluate enzyme activity. We are currently using the human enzyme for coproporphyrinogen oxidase which has been cloned into E coli. The enzyme is purified using affinity chromatography and evaluated by SDS-polyacrylamide gel electrophoresis for purity. Studies to evaluate enzyme molecular weight (by mass spectrometry) with and without covalent modifications are also being done. Collaborative work using site directed mutagenesis of selected amino acids of the cloned coproporphyrinogen oxidase is also a new area into which this research is progressing. An additional area of research is the use of porphyrin derivatives as cytotoxic agents for Leishmania, which are parasitic protozoans that infect more than 350 million people world-wide. We test various porphyrin derivatives for their ability to affect the growth of these protozoans in culture. The long term goal is to develop these derivatives as selective pharmaceutical drugs to treat Leishmania diseases.
Web site: http://www.che.ilstu.edu/people/faculty/jones.htm
Student Qualities: An undergraduate could get involved in research using a cloned, purified enzyme and learn to do enzyme kinetics. They could also learn how to grow and evaluate the Leishmania organisms and the potential cytotoxic effects of selected porphyrin derivatives.
Interested students should have had general chemistry, organic chemistry and be taking or have taken biochemistry and cell biology. They should have a strong interest in biochemical research.
