This Page
› My Interests › Publications
Other Links
› Home › MTSU Home › Biol. Dept. › Pipeline
Contact Me
230A Jones Hall
(615) 494-7621 ofc
(615) 898-5063 fax

My Research Interests

    My laboratory studies the molecular mechanism of zinc metallopeptidases and the regulation of physiological processes, primarily inflammation, by regulated proteolysis by zinc metallopeptidases.  
    Earlier experiments focused on the human puromycin-sensitive aminopeptidase (NPEPPS), a 100 kDa protein that is a member of the M1 family of zinc metallopeptidases.  This family of metallopeptidases possesses the HEXXH(X)18E active site motif, and is distinguished by the lack of an aspartate residue four residues downstream of the distal glutamate.  Previous studies of this enzyme have indicated that the gene encoding ApPS resides on chromosome 17 at 17q12-21, is encoded by 23 exons and 22 introns, and spans roughly 30kb.  The genomic organization of this enzyme is very unlike other members of the M1 family, indicating a unique evolutionary origin.
    Studies on the proteolytic mechanism of NPEPPS indicate that mutation of the active site glutamate (E309) greatly reduces, but does not abolish, catalytic activity.  Substrate binding was unaffected.  These data indicate that E309 acts as a general acid/base catalyst in the hydrolysis of peptide bonds.  Further studies indicate that tyrosine 394 (Y394) helps to stabilize the transition state, but does not act alone; lysine 396 (K396) is a key structural determinant that greatly affects the structural stability and substrate binding of the enzyme.Dr. Thompson at the 2006 ASBMB Meeting
    NPEPPS is involved in many physiological processes, including the processing of antigens for display on class I MHC molecules; processing of neuropeptides involved in pain signalling, growth,  and reproductive function; regulation of the cell cycle and apoptosis; and in normal protein turnover and other general cellular housekeeping functions.  
    Current studies in the laboratory involve the determination of the catalytic mechanism of yeast leukotriene A4hydrolase, characterization of a unique human metallopeptidase of the M1 family, and examination of the interaction of inhibitors with matrix metalloproteinase-2 (MMP-2, gelatinase A).  Other projects in the laboratory include the characterization of a halide ion-binding exosite on NPEPPS and the characterization of RNPEPL1, a novel human aminopeptidase B-like enzyme.

 

top

Publications

  1. Newsome, A.L., Johnson, J.P., Seipelt, R.L., and Thompson, M.W. (2007). Apolactoferrin inhibits the catalytic domain of matrix metalloproteinase-2 by zinc chelation. Biochemistry and Cell Biology 85, 563-572.
  2. Thompson, M.W., Archer, E.D., Romer, C.E., and Seipelt, R.L. (2006).  A conserved tyrosine residue of Saccharomyces cerevisiae leukotriene A4 hydrolase stabilizes the transition state of the peptidase activity.  Peptides 27, 1701-1709.
  3. Thompson, M.W., Govindaswami, M., and Hersh, L.B. (2003). Mutation of active site residues of the puromycin-sensitive aminopeptidase: conversion of the enzyme into a catalytically inactive binding protein. Archives of Biochemistry and Biophysics 413, 236-242.
  4. Thompson, M.W. and Hersh, L.B. (2003). Analysis of conserved residues of the human puromycin-sensitive aminopeptidase. Peptides 24, 1359-1365.
  5. Ma, Z., Daquin, A., Yao, J., Rodgers, D., Thompson, M.W. and Hersh, L.B. (2003). Proteolytic cleavage of the puromycin sensitive aminopeptidase generates a substrate binding domain. Archives of Biochemistry and Biophysics 415, 80-86.
  6. Stoltze, L., Schirle, M., Schwarz, G., Schroter, C., Thompson, M.W., Hersh, L.B., Kalbacher, H., Stevanovic, S., Rammensee, H.G., and Schild, H. (2000). Two new proteases in the MHC class I processing pathway. Nature Immunology 1, 413-418.
  7. Thompson, M.W., Tobler, A.R., Fontana, A., and Hersh, L.B. (1999). Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase. Biochemistry and Biophysical Research Communications 258, 234-240.

Invited Publications
  1. Csuhai, E., Safavi, A., Thompson, M.W., and Hersh, L.B. (1998). Proteolytic inactivation of secreted neuropeptides. In V. Y. H. Hook (Ed.), Proteolytic and Cellular Mechanisms in Prohormone and Proprotein Processing (173-189). Austin, TX: Landes.
  2. Thompson, M.W. and Hersh, L.B. (2004). The puromycin-sensitive aminopeptidase: its role in neurological, reproductive, immunological, and proliferative disorders. In N.M. Hooper and U. Lendeckel (Eds.), Aminopeptidases in Biology and Disease (1-15). New York: Kluwer.

Abstracts
  1. Thompson, M.W., Romer, C. E., and Seipelt, R.L. Two conserved tyrosine residues are essential for the peptidase activity of Saccharomyces cerevisiae leukotriene A4 hydrolase. IUPS/ Experimental Biology 2005 Conference (ASBMB), San Diego, CA, April 2005.
  2. Thompson, M.W., Tobler, A., Fontana, A., and Hersh, L.B. Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase. International Neuropeptide Society's 2000 Summer Neuropeptide Conference, Sainte-Adele, Quebec, Canada, 2000.
  3. Romer, C., Dorset, D., Meyer, C., Thompson, M.W., and Seipelt, R.L. Cloning and Characterization of Yeast Leukotriene A4 Hydrolase. Association of Southeastern Biologists Conference, Memphis, TN, 2004.
  4. Romer, C., Dorset, D., Meyer, C., Thompson, M.W., and Seipelt, R.L. Cloning and Characterization of Yeast Leukotriene A4 Hydrolase. Tennessee Academy of Science/Tennessee Science Teachers Association Meeting, Franklin, TN, 2004.
  5. Thompson, M. W., Romer, C. E., and Seipelt, R. L. Tyrosine 244 Stabilizes the Transition State of the Peptidase Reaction of Saccharomyces cerevisiae Leukotriene A4 Hydrolase. Tennessee Academy of Science Meeting, Martin, TN, 2005.
  6. Archer, E. D., Seipelt, R. L., and Thompson, M. W. A Conserved Tryptophan Residue With an Altered pKa Is Essential for the Peptidase Reaction of Saccharomyces cerevisiae Leukotriene A4 Hydrolase. Tennessee Academy of Science Meeting, Martin, TN, 2005.
  7. Archer, E. D., Seipelt, R. L., and Thompson, M. W. A Conserved Tryptophan Residue With an Altered pKa Is Essential for the Peptidase Reaction of Saccharomyces cerevisiae Leukotriene A4 Hydrolase. ASBMB/ Experimental Biology 2006 Conference, San Francisco, CA, 2006.
  8. Thompson, M. W., Archer, E. D., Terry, A. N., and Seipelt, R. L. Halide ions alter substrate specificity of Saccharomyces cerevisiae leukotriene A4 hydrolase but do not increase catalytic efficiency. ASBMB/ Experimental Biology 2006 Conference, San Francisco, CA, 2006.
  9. Thompson, M. W. and Seipelt, R. L. Arginyl aminopeptidase-like 1 (RNPEPL1) is a ubiquitously expressed, alternatively processed metallopeptidase with preference for neutral and aromatic amino acids. American Society for Cell Biology (ASCB) 2006 Conference, San Diego, CA, December, 2006.