Professor, Biochemistry

B.S. 1970, Central Michigan University
Ph.D. 1982, University of Texas Health Science Center

Email: majone3@ilstu.edu
Phone: (309)438-2366
Office: 320 Science Laboratory Building

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 HPLC 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 an 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 help develop such derivatives as selective pharmaceuticals.

Reaction Catalyzed by Coproporphyrinogen Oxidase:
Conversion of Substrate to Product via Two Oxidative Decarboxylations

SELECTED PUBLICATIONS

J. Morgenthaler, R. Barto, T. Lash, M. Jones, "Use of Di- and Tripropionate substrate analogs to probe the active site of human recombinant coproporphyrinogen oxidase," Medical Science Monitor 2008; 14(1):BR1-7.

J. R. Stephenson, J. A. Stacey, J. B. Morgenthaler, J. A. Friesen, T. D. Lash, and M. A. Jones,  "Role of aspartate 400, arginine 262, and arginine 401 in the catalytic mechanism of human coproporphyrinogen oxidase." Protein Science January 22, 2007.

S. J. Gitter, C. L. Cooper, J. A. Friesen, T. D. Lash, and M. A. Jones. "Investigation of the Catalytic and Structural Roles of Conserved histidines of Human Coproporphyrinogen Oxidase Using Site-directed Mutagenesis." The Medical Science Monitor 13(1):BR1-10, 2007.

J. B. Morgenthaler, J. R. Stephenson, J. A. Friesen, and M. A. Jones. "A Beneficial Alternative to the Traditional Western Blot," American Journal of Biochemistry and Biotechnology 2(4):146-147, 2006.

J. R. Stephenson, J.B. Morgenthaler, C.L. Cooper, J.A. Stacey, J. Momani, E. Jenkins, J.A. Friesen, and M.A. Jones, "Use of iLAP Plates as a New Rapid Screening Method for the Evaluation of Various Coproporphyrinogen Oxidase Mutants,"e Journal of Young Investigators (www.jyi.org/research; online journal sponsored through the NFS) 14, 2006.

C.L. Cooper, T.D. Lash, and M.A. Jones, "Kinetic Evaluation of Coproporphyrinogen Oxidase Using an isomer of the Natural Substrate," Medical Science Monitor 11(11): BR420-425, 2005.

C.L. Cooper, C.M. Stob, M.A. Jones, and T.D. Lash, "Metabolism of Pentacarboxylate Porphyrinogens by Highly Purified Human Coproporphyrinogen Oxidase. Further Evidence for the Existence of an Abnormal Pathway for Heme Biosynthesis." Bioorganic & Medicinal Chemistry 13:6244-6251, 2005.

J.R. Stephenson and M.A. Jones, "Advancement in Fluorescent Detection of Protein Following Electrophoresis," Analytical Biochemistry 346 (2):342-343, 2005.

J.R. Stephenson, N.E. Thomas, J.A. Friesen, and M.A. Jones. "Use of Cross-linking to Assess Subunit Interactions of Recombinant Human Coproporphyrinogen Oxidase." American Journal of Biochemistry and Biotechnology 1(2):103-106, 2005.

M.A. Jones and C.L. Cooper, "Testing Human Saliva for Enzyme Activity: Use of an In-Class Kinetic Experiment for Non-Science Majors in a Large Classroom Setting," The Chemical Educator 10 (2005) 1-3.

M.A. Jones, M. Taneja, Y. Xu, W. Chung, C.M. Stob, and T.D. Lash, "Chromatographic Separation of Chicken Red Blood Cell Coproporphyrinogen oxidase and Uroporphyrinogen Decarboxylase, Two Enzymes in Heme Biosynthesis," Bioorganic & Medicinal Chemistry Letters 14/22 (2004) 5559-5564.

M.A. Jones, R. Shoffner, and J. Friesen, "Use of Computer Modeling of Site-directed Mutagenesis of a Selected Enzyme: A Class Activity for An Introductory Biochemistry Course," Journal of Science Education and Technology, 12 (2003) 413-419.

M.A. Jones, P. Thientanavanich, M. D. Anderson, and T.D. Lash, "Comparison of Two Assay Methods for Activities of Uroporphyrinogen Decarboxylase and Coproporphyrinogen Oxidase," Journal of Biochemical and Biophysical Methods,  55 (2003) 241-249.

M.A. Jones, "Testing the Effect of Meat Tenderizer on Human Hair: A Class Project for Nonscience Majors," Journal of Science Education and Technology, 12 (2003) 39-41.

T.D. Lash, A-S.I.M. Keck, U.N. Mani and M.A. Jones, "Unprecedented Over metabolism of a Porphyrinogen substrate by Copro- porphyrinogen Oxidase. Bioorganic & Medicinal Chemistry Letters, 12 (2002) 1079-1082.

M.A. Jones, J. He, and T.D. Lash, "Kinetic Studies of Novel Di- and Tri-propionate Substrates for the Chicken Red Blood Cell Enzyme Copropor- phyrinogen Oxidase," Journal of Biochemistry, 131 (2002) 201-205.

T.D. Lash, T. A. Kaprak, L. Shen and M. A. Jones, "Metabolism of Analogues of Coproporphyrinogen-III with Modified Side Chains: Implications for Binding at the Active Site of Coproporphyrin- ogen Oxidase", Bioorganic & Medicinal Chemistry Letters, 12 (2002) 181-186.