Home Page for Professor Ben M. Dunn
and his colleagues
University of Florida College of Medicine
Department of Biochemistry and Molecular Biology
Professor Ben M. Dunn earned his Ph.D. in chemistry at the University of California Santa Barbara in 1971 for his work with Dr.Thomas C. Bruice on models for the lysozyme mechanism. Dr. Dunn then examined the mechanism of Staphylococcal nuclease and ribonuclease as a Postdoctoral Associate and a Staff Research Fellow with Dr. Christian B. Anfinsen at the NIH. He subsequently joined the faculty here in 1974, and he was an NIH Career Development Awardee. Dr. Dunn was a member of the NIH Biochemistry Study Section, has organized and presented at numerous international symposia, and has edited a monograph on proteinases that continues to be his major research focus. Dr. Dunn is Editor-in-Chief of Protein and Peptide Letters, Co-Editor of Letters in Peptide Science, Co-Editor of two new volumes on synthetic peptides (Peptide Synthesis Protocols and Peptide Analysis Protocols), and is on the editorial board of Current Protocols in Protein Science, and the Journal of Peptide Research.
Research Interests:
"Understanding the forces which control the specificity and catalytic efficiency of enzymes will contribute to the aim of designing effective and selective drugs and to the goal of designing new enzymes. My laboratory studies the proteolytic enzymes, through the use of site-directed mutagenesis and kinetic analysis with well-defined synthetic oligopeptide substrates. Our studies have revealed important energetic interactions within the active site of enzymes such as the essential proteinase of HIV, the digestive enzyme pepsin, and human cathepsin D. In these studies, we rely on high resolution crystallographic structures to design and interpret experiments."
PUBLICATIONS:
Books Edited
1. Structure and Function of The Aspartic Proteinases: Genetics, Structures and Mechanisms, (1992) Ben M. Dunn, ed., Plenum Press, New York.
2. Peptide Synthesis Protocols, (1994) M.W. Pennington and B.M. Dunn, eds., Vol. 35, Methods in Molecular Biology (John M. Walker, Series Editor), Humana Press, Totowa, N.J., 321 pages.
3. Peptide Analysis Protocols, (1994) B.M. Dunn and M.W. Pennington, eds., Vol. 36, Methods in Molecular Biology (John M. Walker, Series Editor), Humana Press, Totowa, N.J., 335 pages.
4. Current Protocols in Protein Science, (1995) J.E. Coligan, B.M. Dunn, H.L. Ploegh, D.W. Speicher, P.T. Wingfield, eds. (V. Chanda, Series Editor), John Wiley & Sons, New York, ca. 800 pages.
Chapters in Books
16. B.M. Dunn, J. Kay, A. Gustchina and A. Wlodawer (1994) "Subsite Preferences of Retroviral Proteinases" in Methods in Enzymology: Retroviral Proteases, L.C. Kuo and J.A. Shafer, eds., Academic Press, p. 254-278, plus 8 color plates.
19. B.M. Dunn, P.E. Scarborough, W.T. Lowther, and C. Rao-Naik (1995) "Comparison of the Active Site Specificity of the Aspartic Proteinases Based on a Systematic Series of Peptide Substrates" in: Aspartic Proteinases: Proceedings of the 5th International Conference, (K. Takahashi, Ed.), Plenum Press, pp. pp. 1-9.
30. B. M. Dunn, Kohei Oda, John Kay, Chetana Rao-Naik, W. Todd Lowther, Brian M. Beyer,
Paula E. Scarborough and Marina Bukhtiyarova (1997), "Comparison o the Specificity of the Aspartic
Proteinases Towards Internally-Consistent Sets of Oligopeptide Substrates", in VIIth Aspartic
Proteinase Conference, Michael N. G. James, ed., Plenum Press, New York, in press.
REFEREED PUBLICATIONS
[1992-1997]
67. C.M. Rao, P.E. Scarborough, J. Kay, B. Batley, S. Rapundalo, S. Klutchko, M.D. Taylor, E.A. Lunney, C.C. Humblet and B.M. Dunn (1993) "Specificity in the Binding of Inhibitors to the Active Site of Human/Primate Aspartic Proteinases-Analysis of P2-P1-P1'-P2' Variation," J. Med. Chem., 36:2614-2620.
68. J. Cooper, W. Quail, C. Frazao, S.I. Foundling, T.L. Blundell, C. Humblet, E.A. Lunney, W. T. Lowther and B.M. Dunn (1992) "X-ray Crystallographic Analysis of Inhibtion of Endothiapepsin by Cyclohexyl Renin Inhibitors," Biochemistry, 31:8142-8150.
69. L.H. Phylip, J.S. Mills, B.F. Parten, B.M. Dunn and J. Kay (1992) "Intrinsic Activity of Precursor Forms of HIV-1 Proteinase," FEBS Letts., 314: 449-454.
70. J.T. Griffiths, L.A. Tomchak, J.S. Mills, M.C. Graves, N.D. Cook, B.M. Dunn and J. Kay (1994) "Interactions of Substrates and Inhibitors with a Family of Tethered HIV-1 and HIV-2 Homo- and Heterodimeric Proteinases", J. Biol. Chem., 269:4787-4793.
71. E.A. Lunney, H.W. Hamilton, J.C. Hodges, J.S. Kaltenbronn, J.T. Repine, M. Badasso, J.B. Cooper, C. Dealwis, B.A. Wallace, W.T. Lowther, B.M. Dunn and C. Humblet (1993) "Analyses of Ligand Binding in Five Endothiapepsin Crystal Complexes and Their Use in the Design and Evaluation of Novel Renin Inhibitors," J. Med. Chem., 36, 3809-3820.
72. J. Dame, C. Berry, B.M. Dunn and J. Kay (1994) "An Aspartic Proteinase from the Human Malaria Parasite Plasmodium falciparum HB3," Mol. and Biochem. Parasitology, 64:177-190.
73. P.E. Scarborough and B.M. Dunn (1994) "Redesign of the Substrate Specificity of Human Cathepsin D: The Dominant Role of Position 287 in the S2 Subsite," Protein Engineering, Vol. 7, No. 4, pp. 495-502.
74. T.K. Sawyer, J.F. Fisher, J.B. Hester, C.W. Smith, A.G. Tomasselli, W.G. Tarpley, P.S. Burton, J.O. Hui, T.J. McQuade, R.A. Conradi, V.S. Bradford, L. Liu, J.H. Kinner, J. Tustin, D.L. Alexander, A.W. Harrison, D.E. Emmert, D.J. Staples, L.L. Maggiora, Y.Z. Zhang, R.A. Poorman, B.M. Dunn, C. Rao, P.E. Scarborough, W.T. Lowther, C. Craik, D. DeCamp, J. Moon, W.J. Howe, and R. L. Heinrikson (1993) "Peptidomimetic Inhibitors of Human Immunodeficiency Virus Protease (HIV-PR): Design, Enzyme Binding and Selectivity, Antiviral Efficacy, and Cell Permeability Properties," Bioorganic & Medicinal Chemistry Letters, Vol. 3, No. 5, pp. 819-824.
75. Y. Lin, X. Lin, L. Hong, S. Foundling, R.L. Heinrikson, S. Thaisrivongs, W. Leelamanit, D. Raterman, M. Shah, B.M. Dunn and J. Tang (1995) "Effect of Point Mutations on the Kinetics and the Inhibition of Human Immunodeficiency Virus Type 1 Protease: Relationship to Drug Resistance, Biochemistry 34, 1143- 1152.
76. P.J.H. Johansson, C. Malone, W. Swietnicki, B.M. Dunn and R.C. Williams (1994) "Fv Structure of Monoclonal Antibody II-481 Against Herpes Simplex Virus Fc - Binding Glycoprotein gE Contains Immunodominant CDR Epitopes which React with Human IgM Rheumatoid Factors", J. Exp. Med., Vol. 180, 1873-1888.
77. W.T. Lowther and B.M. Dunn (1994) "Kinetics of Enzyme-Catalyzed Oligopeptide Cleavage Monitored by Capillary Electrophoresis: Comparison to Spectrophotometric and HPLC Methods", Letters in Peptide Science, Vol. 1, 89- 94.
78. J. Hill, L. Tyas, L.H. Phylip, J. Kay, B.M. Dunn and C. Berry (1994) "High Level Expression and Characterization of Plasmepsin II, an Aspartic Proteinase from Plasmodium falciparum", FEBS Letts., 352, Vol 2, 155-158.
79. C. Rao-Naik, K. Guruprasad, B. Batley, S. Rapundalo, J. Hill, T. Blundell, J. Kay and B.M. Dunn (1995) "Exploring the Binding Preferences/Specificity in the Active Site of Human Cathepsin E", Proteins: Structure, Function, and Genetics 22, 168-181.
80. B.P. Holskin, M. Bukhtiyarova, B.M. Dunn, P. Baur, J. de Chastonay and M.W. Pennington (1995) "Fluorescence-based Assay of Human Cytomegalovirus Proteinase Using a Peptide Substrate", Analytical Biochem. 227, 148-155.
81. W.T. Lowther, Pavel Majer and B.M. Dunn (1995) "Engineering the Substrate Specificity of Rhizopuspepsin: The Role of Asp 77 of Fungal Aspartic Proteinases in Facilitating the Cleavage of Oligopeptide Substrates with Lysine in P1", Protein Science 4, 689-702.
82. A. Wlodawer, A. Gustchina, L. Reshetnikova, J. Lubkowski, A. Zdanov, K.Y. Hui, E.L. Angleton, W.G. Farmerie, M.M. Goodenow, D. Bhatt, L. Zhang and B.M. Dunn (1995) "Structure of an Inhibitor Complex of the Protease from Feline Immunodeficiency Virus", Nature Structural Biology 2, 480-488.
83. S.D. Fowler, J. Kay, B.M. Dunn and P.J. Tatnell (1995) "Monomeric human cathepsin E", FEBS Letters 366, 72-74.
84. K.A. Barrie, E.E. Perez, S.L. Lamers, W.G. Farmerie, B.M. Dunn, J.W. Sleasman and M.M. Goodenow (1996) "Amino Acid Substitutions in HIV-1 Protease, Gag p7 and p6, and Protease Cleavage Sites within Gag/Pol Polyproteins in the Absence of Protease Inhibitors in Mothers and Children infected by Human Immunodeficiency Virus Type 1", Virology 219, 407-416.
85. B. Beyer and B. M. Dunn (1996) "Self-Activation of Recombinant Human Lysosomal Procathepsin D at a Newly Engineered Cleavage Junction: "Short" Pseudocathepsin D", J. Biol. Chem., 271, 15590-15596.
86. Li Zhang, P. Baur, M.E. Byrnes, M.W. Pennington, J. de Chastonay and B.M. Dunn, (1997) "Binding of Mutant HIV-1 Proteases With Junction B Peptides Containing Methyleneamino Isostere Replacements", Protein and Peptide Letters, in press..
87. H. Kondo, Y. Shibano, T. Amachi, K. Oda, and B.M. Dunn (1995) "Substrate specificities and kinetic properties of Proteinase A from Saccharomyces cerevisiae and development of its sensitive fluorescent substrate", in revision.
88. W.T. Lowther and B.M. Dunn (1996) The Promiscuous Active Site Specificity/Binding Preferences of the Fungal Aspartic Proteinase, Rhizopuspepsin", submitted.
90. David J. Powell, Daniel Bur, Alexander Wiodawer, Alla Gustchina, Susan L. Payne, Ben M. Dunn and John Kay (1996) "Expression, Characterisation and Mutagenesis of the Aspartic Proteinase from Equine Infectious Anaemia Virus", European J. Biochem., 241, 664-674.
91. C. Rao-Naik and B. M. Dunn (1966) "Role of Glu-13 in the pH-Dependent Specificity of Porcine Pepsin", manuscript in preparation.
92. J. Westling, C. A. Yowell, P. Majer, J. W. Erickson, J. B. Dame, and B. M. Dunn (1997) "Plasmodium falciparum , P. vivax, and P. malariae": A Comparison of the Active Site Properties of Plasmepsins Cloned and Expressed from Three Different Species of the Malaria Parsite", Experimental Parasitology, submitted for a special issue.
93. C. Rao-Naik and B. M. Dunn (1996) "Role of Glu-287 in the pH-Dependent Specificity of Porcine Pepsin", manuscript in preparation.
94. C. Rao-Naik, J. Zalatoris, M. Barman, M. Banull, R. Rogers, W. G. Farmerie, J. Kay and B. M. Dunn (1996) "Cloning, Expression, Purification and Preliminary Characterization of the Recombinant Pepsin Inhibitor from Ascaris suum", submitted
95. M. Ito, B. M. Dunn, and K. Oda (1996) "Substrate Specificities of Pepstatin- Insensitive Carboxyl Proteinases from Gram-negative Bacteria", J. Biochem. (Tokyo), 120, 845-850.
96. S. I. Wilson, L. H. Phylip, J. S. Mills, S. Gulnik, John W. Erickson, B. M. Dunn, and J. Kay (1997) "Escape Mutants of HIV-1 Proteinase: Enzymic Efficiency and Susceptibility to Inhibition, Biochim. Biophys. Acta, 1339, 113-125.
97. B. M. Beyer and B. M. Dunn (1997) "Prime Region Subsite Specificity Characterization
of Human Cathepsin D: The Dominant Role of Position 128", submitted.
REVIEWS
1. B.M. Dunn and T.C. Bruice, (1973) "Physical Organic Models for the Mechanism of Lysozyme Action," in Advances in Enzymology, A. Meister, ed., Wiley- Interscience, 37: 1-78.
2. B.M. Dunn, (1984) "The Study of Ligand-Protein Interactions Utilizing Affinity Chromatography," App. Biochem. and Biotech., 9: 261-284.
3. J. Kay and B.M. Dunn, (1990) "Viral Proteinases: Weakness in Strength," Biochem. Biophys. Acta (Gene Structure and Expression), 1048: 1-18.
4. Ben M. Dunn (1992) "Reaction Mechanisms of the Proteolytic Enzymes," in Advances in Detailed Reaction Mechanisms Volume 2 Mechanism of Biological Importance J. Coxon, ed., JA1 Press, Greenwich, Connecticut, pp 213-241.
-William A. Gilbert: Sept. 1975 - June 1978. Ph.D. June 1978 "Quantitative
Affinity Chromatography of Chymotrypsin"
-Mark Carter: Dec. 1984 - Aug. 1987, Ph.D. - Aug. 1987 "Assessment of Binding Domains of Mouse Interferon Gamma Using Synthetic Peptides and Antibodies"
-Mike Pennington: March 1985 - Nov. 1988. Ph.D. Dec 1988 "Structure- Function Relationships of the Major Neurotoxin From the Sea Anemone Stichodactyla Helianthus with a New Sodium Channel Receptor Site"
-Jeff Weidner: Sept. 1984 - Dec. 1989 Ph.D. Dec 1989 "Development of Synthetic peptide Substrates for the Poliovirus 3C Proteinase"
-Paula Scarborough: Jan. 1989 - Aug. 1993. Ph.D. Aug. 1993 "Unique Active Site Specificity of Human Cathepsin D as Studied Through Kinetics, Molecular Modeling, and Residue-Specific Mutagenesis"
-Chetana Rao: Feb. 1990 - Aug. 1994. Ph.D. Aug. 1994 "A Detailed Investigation into the Enzymatic Specificity of Porcine Pepsin"
-Todd Lowther: Feb. 1990 - Aug. 1994. Ph.D. Aug. 1994 "Site-Directed Mutagenesis of the Aspartic Proteinase Rhizopuspepsin: An Analysis of Unique Specificity"
-Wieslaw Swietnicki: Feb. 1990 - August 1995 Ph. D. Aug. 1995 "Specificity of Hepatitis A 3C Protease"
-Wichet Leelamanit: May 1992 - May 1996 Ph.D. May 1996 "Kinetic Analysis and Inhibitor Susceptibility of Naturally- occurring Human Immunodeficiency Virus Type 1 proteinase variants"
-Brian Beyer: May 1993 - December 1996 Ph.D. December 1996 "Exploration of Human Cathepsin D Specificity Using Native Enzyme, A Re-Engineered Recombinant Model, and Site-Directed Mutagenesis"
-Deepa Bhatt: March 1994 -
-Jennifer Westling: March 1994 -
-Greg Bloom: March 1994 -
-Jeff Zalatoris: March 1995 -
File last updated on July 3, 1997.