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David Johnson, Ph.D.
Department of Biomedical Sciences
Stanton Gerber Hall
Office: Bldg. 178; VA campus, Room A105
Lab: Bldg. 178, A104
- 1967 B.S. in Chemistry, University of Memphis
- 1973 Ph.D. in Chemistry, University of Memphis
- 1978 Post-Doctoral in Biochemistry, University of Georgia (Athens)
Protein Structure and Function, Enzymology, Proteomics, Blood Proteins, Human serine proteases and their inhibitors.
Founding faculty: Quillen College of Medicine-1978 and Gatton College of Pharmacy-2007
Research deals with proteolytic enzymes and their inhibitors, including protein purification, characterization, sequencing, structure function relationships, kinetics, and regulation. Particular emphasis is placed on the roles of proteases and inhibitors in the pathogenesis of human diseases. Work on the structure of human alpha-1-proteinase inhibitor led to the discovery of its active site and we showed that oxidation of a methionine residue in the inhibitory site of α1-PI caused the loss of elastase inhibitory activity. This finding resulted in the hypothesis that oxidants can lead to a lung-localized inhibitor deficiency. A deficiency of α1-PI, which normally inhibits neutrophil elastase, is known to cause emphysema. This led to studies of the reactions of ozone and nitrogen dioxide on the function of human α1-PI and the secretory leukocyte proteinase inhibitor found in human bronchial mucus, which also inhibits neutrophil elastase. Another long-standing project focuses on the structure and function of human mast cell tryptase, an unusual serine protease that is the most abundant protein in mast cells. Recently, tryptase has been shown to activate protease zymogens, suggesting a critical role in tumor growth and the pathogenesis of arthritis. Pichia pastoris has been used to expression of recombinant human mast cell and neutrophil serine proteases, as well as human enterokinase and C-reactive protein.
David Johnson and James Travis. Structural Evidence for Methionine at the reactive Site of Human Alpha-1-Proteinase Inhibitor. J. Biol. Chem. 253. 7142-7144 (1978)
David Johnson and James Travis. The Oxidative Inactivation of Human Alpha-1-Proteinase Inhibitor: Further Evidence for Methionine at the Reactive Center. J. Biol. Chem. 254, 4022-4026 (1979)
Sanjay K. Singh, Avinash Thirumalai, David J. Hammond, Jr., Michael K. Pangburn, Vinod K. Mishra, David A. Johnson, Antonio E. Rusiñol, and Alok Agrawal Exposing a hidden functional site of C-reactive protein by site-directed mutagenesis J.Biol.Chem. 287, 3550–3558, 2012.
Eliot T. Smith and David A. Johnson, Human Enteropeptidase Light Chain: Bioengineering of Recombinants and Kinetic Investigations of Structure and Function Protein Science 22, 577-585, 2013.
Eliot T. Smith, Evan T. Perry, Megan B. Sears, David A. Johnson. Expression of recombinant human mast cell chymase with Asn-linked glycans in glycoengineered Pichia pastoris. Protein Expr Purif. 2014 Oct;102:69-75.