Professor John B Dame Department of Pathobiology University of Florida P.O. Box 110880, Gainesville, FL 32605, USA Email: damej@mail.vetmed.ufl.edu Tel: 1-352-392-4700 ext 5818 Fax: 1-352-392-9704 Homepage: http://www.vetmed.ufl.edu/path/dame.htm Research Plasmepsins are a family of ten aspartic proteases found in the human malaria parasite, Plasmodium falciparum. Four of these enzymes are found in the digestive vacuole where they are involved in hemoglobin digestion. The other six enzymes appear to be localized in other subcellular locations or in stages of the parasite life cycle other than the asexual erythrocytic stage. Genes encoding the digestive vacuole plasmepsins of all four human malaria parasites P. falciparum, P. vivax, P. malariae, and P. ovale have been cloned and expressed in our laboratory. The metabolic functions of each are being characterized using classical enzyme kinetic studies, crystallography and genetics. Crystal structures and computer-generated models of these enzymes are used in combination with enzyme kinetic studies using panels of peptide substrates and peptidomimetic inhibitors to characterize the distinctive features of the active site binding cleft. Knockout mutants, each lacking one or more of the four digestive vacuole plasmepsins of P. falciparum, have been produced and are currently being studied to examine the role of each enzyme in hemoglobin digestion and other cellular functions. Collaborations Ben M. Dunn Dept. of Biochemistry and Molecular Biology University of Florida Gainesville, FL USA Mavis Agbandje-McKenna Dept. of Biochemistry and Molecular Biology University of Florida Gainesville, FL USA Robert McKenna Dept. of Biochemistry and Molecular Biology University of Florida Gainesville, FL USA David A. Fidock Dept. of Microbiology and Immunology Albert Einstein College of Medicine Bronx, NY USA Joseph M. Vinetz Dept. of Medicine University of California San Diego, CA USA Publications Dame, J. B., G. R. Reddy, C. A. Yowell, B. M. Dunn, J. Kay, and C. Berry. 1994. Sequence, Expression and Modeled Structure of An Aspartic Proteinase from the Human Malaria Parasite Plasmodium falciparum. Molecular and Biochemical Parasitology 64:177-190.   Bernstein, N. K., M. M. Cherney, C. A. Yowell, J. B. Dame, and M. N. G. James. 2003. Structural insights into the activation of P. vivax plasmepsin. Journal of Molecular Biology 329:505-524. Dame, J.B., C.A. Yowell, A.L. Omara-Opyene, J.M. Carlton, R.A. Cooper, and T. Li. 2003. Plasmepsin 4, the food vacuole aspartic proteinase found in all Plasmodium spp. infecting man. Mol. Biochem. Parasitol. 130:1-12. Brown, W.M., C.A. Yowell, A. Hoard, T.A. Vander Jagt, L.A. Hunsaker, L.M. Deck, R.E. Royer, R.C. Piper, J.B. Dame, M.T. Makler, and D.L. Vander Jagt. 2004. Comparative Structural Analysis and Kinetic Properties of Lactate Dehydrogenases from the Four Species of Human Malarial Parasites. Biochemistry 43:6219-6229. Li, T., C.A., Yowell, B.B.Beyer, S.-H. Hung, J. Westling, M.T. Lam, B.M. Dunn, J.B.Dame. 2004. Recombinant expression and enzymatic subsite characterization of plasmepsin 4 from the four Plasmodium species infecting man. Mol.Biochem.Parasitol. 135: 101-109. Questions/suggestions? Please contact the Network Administrator. Copyright © by International Protease Network All Right Reserved.