József Tőzsér
CURRENT APPOINTMENT(S):
Professor of Biochemistry and Molecular Biology, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary (2003-)
Head of the Laboratory of Retroviral Biochemistry, Reseach Center for Molecular Medicine, Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, University of Debrecen, Debrecen, Hungary (1993)
Head of the Proteomics Core Facility, Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary (2005-)
Adjunct professor of the Department of Biology, Georgia State University, Atlanta, Georgia, USA
CONTACTS:
Office address: Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
Street address: Life Science Building, Room #3.103, Egyetem tér 1, Debrecen, Hungary
Postal address: Egyetem tér 1, POB 6, Debrecen, Hungary, H-4012
Phone: +36-52-416432
Fax: +36-52-314989
Web: Laboratory of Retroviral Biochemistry
GENERAL INFORMATION:
Languages:
Hungarian (native)
English (State Exam, Intermediate Level, Type C, Á40215/1984, Debrecen, 1984
Russian (State Exam, Base Level, AÁ 09263/1985, Debrecen, 1985
ACADEMIC BACKGROUND:
Dr. Habil, Faculty of Medicine, University of Debrecen, Hungary (2002)
D.Sc. in Biology, Hungarian Academy of Sciences (2002). Thesis: Study of wild-type and mutant retroviral proteases (in Hungarian)
C.Sc in Biology, Hungarian Academy of Sciences (1994). Thesis: Study of the substrate specificity of retroviral proteases using oligopeptide substrates (in Hungarian) advisor: Dr. Stephen Oroszlan.
Postdoctoral Fellow, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland, USA, (1989-1991) advisor: Dr. Stephen Oroszlan.
Dr. Univ., University Medical School of Debrecen, Hungary (1988). Thesis: Neutral proteinases and proteinase inhibitors in human tears (in Hungarian) advisor: Dr. Pál Elödi
M.Sc. in Chemistry, Lajos Kossuth University of Art and Science, Debrecen, Hungary (1983). Thesis: Mixed-ligand compex formation in copper (II)-L-seryl-gycine and copper (II)-triglycine-B ligand systems (in Hungarian, advisor: Dr. Etelka Farkas)
Undergraduate student in Chemistry, Lajos Kossuth University of Art and Science, Debrecen, Hungary (1978-1983).
SCIENTIFIC BACKGROUND:
Associate Professor, Department of Biochemistry and Molecular Biology, Faculty of Medicine, Debrecen University (University Medical Scool of Debrecen till 2000), Hungary (1997-2003)
Senior Lecturer, Department of Biochemistry, University Medical School of Debrecen, Debrecen, Hungary (1993-1997)
Assistant Lecturer, Department of Biochemistry, Medical University of Debrecen, Debrecen, Hungary (1991-1993)
Research Associate of the Hungarian Academy of Science, Biochemistry Instructor for Medical Students in Department Biochemistry, Medical University of Debrecen, Hungary (1988-1989)
Research Consultant, Department of Blood Fractionation, National Institute of Hematology and Blood Transfusion, Budapest, Hungary. (1987-1989)
Research Fellow, Biochemistry Instructor for Medical Students, Department of Biochemistry, Medical University of Debrecen, Hungary (1983-1988)
CURRENT MEMBERSHIPS IN PROFESSIONAL SOCIETIES:
Hungarian Biochemical Society, Hungary, member since 1992.
Hungarian Biological Society, Hungary, member since 1992.
Hungarian Proteomics Society, founding member since 2006.
AWARDS:
Istvan Szechenyi Fellowship (2001-2003)
Szechenyi Professorship (1998 – 2001)
Outstanding Teacher of the Faculty of Medicine, Debrecen University, Hungary (2006)
PATENTS:
2001
Csutak, A., Berta, A., Tőzsér, J., Silver, D. (2001) Plasminogen activator to prevent corneal and subepithelial hase after laser vision corresction surgery. Patent application PCT/US01/31849.
1997
Aradi, J., D.Tóth, F., Fésüs, L., Tőkés, S., Tőzsér, J., Nagy, K., Uray, I., Várnai, P., Mező, I. (1997) Anti-HIV activity of medicinal plant extract and its compounds with therapeutic and curative effect. Patent PHT HU 97000 15.
PUBLICATIONS:
2006
Tozser, J., Shulenin, S., Young, M. R., Briggs, C. J., and Oroszlan, S. (2006). Replication-dependent fitness recovery of Human immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein. J Gen Virol 87, 961-965.
Sperka, T., Boross, P., Eizert, H., Tozser, J., and Bagossi, P. (2006). Effect of mutations on the dimer stability and the pH optimum of the human foamy virus protease. Protein Eng Des Sel 19, 369-375.
Mitchell, M. S., Tozser, J., Princler, G., Lloyd, P. A., Auth, A., and Derse, D. (2006). Synthesis, processing, and composition of the virion-associated HTLV-1 reverse transcriptase. J Biol Chem 281, 3964-3971.
Feher, A., Boross, P., Sperka, T., Miklossy, G., Kadas, J., Bagossi, P., Oroszlan, S., Weber, I. T., and Tozser, J. (2006). Characterization of the murine leukemia virus protease and its comparison with the human immunodeficiency virus type 1 protease. J Gen Virol 87, 1321-1330.
Fang, B., Boross, P. I., Tozser, J., and Weber, I. T. (2006). Structural and kinetic analysis of caspase-3 reveals role for s5 binding site in substrate recognition. J Mol Biol 360, 654-666.
Boross, P., Tozser, J., and Bagossi, P. (2006). Improved purification protocol for wild-type and mutant human foamy virus proteases. Protein Expr Purif 46, 343-347.
2005
Tozser, J., Tropea, J. E., Cherry, S., Bagossi, P., Copeland, T. D., Wlodawer, A., and Waugh, D. S. (2005). Comparison of the substrate specificity of two potyvirus proteases. Febs J 272, 514-523.
Tie, Y., Boross, P. I., Wang, Y. F., Gaddis, L., Liu, F., Chen, X., Tozser, J., Harrison, R. W., and Weber, I. T. (2005). Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs. Febs J 272, 5265-5277.
Sperka, T., Pitlik, J., Bagossi, P., and Tozser, J. (2005). Beta-lactam compounds as apparently uncompetitive inhibitors of HIV-1 protease. Bioorg Med Chem Lett 15, 3086-3090.
Liu, F., Boross, P. I., Wang, Y. F., Tozser, J., Louis, J. M., Harrison, R. W., and Weber, I. T. (2005). Kinetic, stability, and structural changes in high-resolution crystal structures of HIV-1 protease with drug-resistant mutations L24I, I50V, and G73S. J Mol Biol 354, 789-800.
Bagossi, P., Horvath, G., Vereb, G., Szollosi, J., and Tozser, J. (2005). Molecular modeling of nearly full-length ErbB2 receptor. Biophys J 88, 1354-1363.
Bagossi, P., Sperka, T., Feher, A., Kadas, J., Zahuczky, G., Miklossy, G., Boross, P., and Tozser, J. (2005). Amino acid preferences for a critical substrate binding subsite of retroviral proteases in type 1 cleavage sites. J Virol 79, 4213-4218.
2004
Tozser, J., Shulenin, S., Louis, J. M., Copeland, T. D., and Oroszlan, S. (2004). In vitro processing of HIV-1 nucleocapsid protein by the viral proteinase: effects of amino acid substitutions at the scissile bond in the proximal zinc finger sequence. Biochemistry 43, 4304-4312.
Nallamsetty, S., Kapust, R. B., Tozser, J., Cherry, S., Tropea, J. E., Copeland, T. D., and Waugh, D. S. (2004). Efficient site-specific processing of fusion proteins by tobacco vein mottling virus protease in vivo and in vitro. Protein Expr Purif 38, 108-115.
Mahalingam, B., Wang, Y. F., Boross, P. I., Tozser, J., Louis, J. M., Harrison, R. W., and Weber, I. T. (2004). Crystal structures of HIV protease V82A and L90M mutants reveal changes in the indinavir-binding site. Eur J Biochem 271, 1516-1524.
Kadas, J., Weber, I. T., Bagossi, P., Miklossy, G., Boross, P., Oroszlan, S., and Tozser, J. (2004). Narrow substrate specificity and sensitivity toward ligand-binding site mutations of human T-cell Leukemia virus type 1 protease. J Biol Chem 279, 27148-27157.
Feher, A., Boross, P., Sperka, T., Oroszlan, S., and Tozser, J. (2004). Expression of the murine leukemia virus protease in fusion with maltose-binding protein in Escherichia coli. Protein Expr Purif 35, 62-68.
Csutak, A., Silver, D. M., Tozser, J., Hassan, Z., and Berta, A. (2004). Urokinase-type plasminogen activator to prevent haze after photorefractive keratectomy, and pregnancy as a risk factor for haze in rabbits. Invest Ophthalmol Vis Sci 45, 1329-1333.
Bagossi, P., Kadas, J., Miklossy, G., Boross, P., Weber, I. T., and Tozser, J. (2004). Development of a microtiter plate fluorescent assay for inhibition studies on the HTLV-1 and HIV-1 proteinases. J Virol Methods 119, 87-93.
2003
Tozser, J., Bagossi, P., Zahuczky, G., Specht, S. I., Majerova, E., and Copeland, T. D. (2003). Effect of caspase cleavage-site phosphorylation on proteolysis. Biochem J 372, 137-143.
Tozser, J., Shulenin, S., Kadas, J., Boross, P., Bagossi, P., Copeland, T. D., Nair, B. C., Sarngadharan, M. G., and Oroszlan, S. (2003). Human immunodeficiency virus type 1 capsid protein is a substrate of the retroviral proteinase while integrase is resistant toward proteolysis. Virology 310, 16-23.
Tozser, J., and Oroszlan, S. (2003). Proteolytic events of HIV-1 replication as targets for therapeutic intervention. Curr Pharm Des 9, 1803-1815.
Tozser, J. (2003). Stages of HIV replication and targets for therapeutic intervention. Curr Top Med Chem 3, 1447-1457.
Csutak, A., Silver, D. M., Tozser, J., Facsko, A., and Berta, A. (2003). Plasminogen activator activity and inhibition in rabbit tears after photorefractive keratectomy. Exp Eye Res 77, 675-680.
2002
Mahalingam, B., Boross, P., Wang, Y. F., Louis, J. M., Fischer, C. C., Tozser, J., Harrison, R. W., and Weber, I. T. (2002). Combining mutations in HIV-1 protease to understand mechanisms of resistance. Proteins 48, 107-116.
Kapust, R. B., Tozser, J., Copeland, T. D., and Waugh, D. S. (2002). The P1' specificity of tobacco etch virus protease. Biochem Biophys Res Commun 294, 949-955.
Feher, A., Weber, I. T., Bagossi, P., Boross, P., Mahalingam, B., Louis, J. M., Copeland, T. D., Torshin, I. Y., Harrison, R. W., and Tozser, J. (2002). Effect of sequence polymorphism and drug resistance on two HIV-1 Gag processing sites. Eur J Biochem 269, 4114-4120.
2001
Tozser, J. (2001). HIV inhibitors: problems and reality. Ann N Y Acad Sci 946, 145-159.
Kapust, R. B., Tozser, J., Fox, J. D., Anderson, D. E., Cherry, S., Copeland, T. D., and Waugh, D. S. (2001). Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency. Protein Eng 14, 993-1000.
Ishima, R., Ghirlando, R., Tozser, J., Gronenborn, A. M., Torchia, D. A., and Louis, J. M. (2001). Folded monomer of HIV-1 protease. J Biol Chem 276, 49110-49116.
Gaspar, R., Jr., Bagossi, P., Bene, L., Matko, J., Szollosi, J., Tozser, J., Fesus, L., Waldmann, T. A., and Damjanovich, S. (2001). Clustering of class I HLA oligomers with CD8 and TCR: three-dimensional models based on fluorescence resonance energy transfer and crystallographic data. J Immunol 166, 5078-5086.
2000
Zahuczky, G., Boross, P., Bagossi, P., Emri, G., Copeland, T. D., Oroszlan, S., Louis, J. M., and Tozser, J. (2000). Cloning of the bovine leukemia virus proteinase in Escherichia coli and comparison of its specificity to that of human T-cell leukemia virus proteinase. Biochim Biophys Acta 1478, 1-8.
Tozser, J., Zahuczky, G., Bagossi, P., Louis, J. M., Copeland, T. D., Oroszlan, S., Harrison, R. W., and Weber, I. T. (2000). Comparison of the substrate specificity of the human T-cell leukemia virus and human immunodeficiency virus proteinases. Eur J Biochem 267, 6287-6295.
Louis, J. M., Weber, I. T., Tozser, J., Clore, G. M., and Gronenborn, A. M. (2000). HIV-1 protease: maturation, enzyme specificity, and drug resistance. Adv Pharmacol 49, 111-146.
Csutak, A., Tozser, J., Bekesi, L., Hassan, Z., Berta, A., and Silver, D. M. (2000). Plasminogen activator activity in tears after excimer laser photorefractive keratectomy. Invest Ophthalmol Vis Sci 41, 3743-3747.
1999
Tozser, J., Bagossi, P., Boross, P., Louis, J. M., Majerova, E., Oroszlan, S., and Copeland, T. D. (1999). Effect of serine and tyrosine phosphorylation on retroviral proteinase substrates. Eur J Biochem265, 423-429.
Skuta, G., Fischer, G. M., Janaky, T., Kele, Z., Szabo, P., Tozser, J., and Sumegi, B. (1999). Molecular mechanism of the short-term cardiotoxicity caused by 2',3'-dideoxycytidine (ddC): modulation of reactive oxygen species levels and ADP-ribosylation reactions. Biochem Pharmacol 58, 1915-1925.
Louis, J. M., Oroszlan, S., and Tozser, J. (1999). Stabilization from autoproteolysis and kinetic characterization of the human T-cell leukemia virus type 1 proteinase. J Biol Chem 274, 6660-6666.
Fenyofalvi, G., Bagossi, P., Copeland, T. D., Oroszlan, S., Boross, P., and Tozser, J. (1999). Expression and characterization of human foamy virus proteinase. FEBS Lett 462, 397-401.
Briggs, C. J., Ott, D. E., Coren, L. V., Oroszlan, S., and Tozser, J. (1999). Comparison of the effect of FK506 and cyclosporin A on virus production in H9 cells chronically and newly infected by HIV-1. Arch Virol 144, 2151-2160.
Boross, P., Bagossi, P., Copeland, T. D., Oroszlan, S., Louis, J. M., and Tozser, J. (1999). Effect of substrate residues on the P2' preference of retroviral proteinases. Eur J Biochem 264, 921-929.
1998
Tozser, J., and Berta, A. (1998). Lactate dehydrogenase activity in pathological human tears obtained with glass capillaries correlates with the albumin content. Int Ophthalmol 22, 289-292.
Takacs, L., Boross, P., Tozser, J., Modis, L., Jr., Toth, G., and Berta, A. (1998). Transforming growth factor-beta induced protein, betaIG-H3, is present in degraded form and altered localization in lattice corneal dystrophy type I. Exp Eye Res 66, 739-745.
Bagossi, P., Cheng, Y. S., Oroszlan, S., and Tozser, J. (1998). Comparison of the specificity of homo- and heterodimeric linked HIV-1 and HIV-2 proteinase dimers. Protein Eng 11, 439-445.
1997
Tozser, J. (1997). Specificity of Retroviral Proteinases Based on Substrates Containing Tyrosine and Proline at the Site of Cleavage. Pathol Oncol Res 3, 142-146.
Tozser, J., Yin, F. H., Cheng, Y. S., Bagossi, P., Weber, I. T., Harrison, R. W., and Oroszlan, S. (1997). Activity of tethered human immunodeficiency virus 1 protease containing mutations in the flap region of one subunit. Eur J Biochem 244, 235-241.
Tozser, J., Bagossi, P., Weber, I. T., Louis, J. M., Copeland, T. D., and Oroszlan, S. (1997). Studies on the symmetry and sequence context dependence of the HIV-1 proteinase specificity. J Biol Chem272, 16807-16814.
1996
Tozser, J., Bagossi, P., Weber, I. T., Copeland, T. D., and Oroszlan, S. (1996). Comparative studies on the substrate specificity of avian myeloblastosis virus proteinase and lentiviral proteinases. J Biol Chem 271, 6781-6788.
Briggs, C. J., Tozser, J., and Oroszlan, S. (1996). Effect of cyclosporin A on the replication cycle of human immunodeficiency virus type 1 derived from H9 and Molt-4 producer cells. J Gen Virol 77 ( Pt 12), 2963-2967.
Bogati, M. S., Pocsi, I., Maticsek, J., Boross, P., Tozser, J., and Szentirmai, A. (1996). NADP-specific glutamate dehydrogenase of Penicillium chrysogenum has a homohexamer structure. J Basic Microbiol36, 371-375.
Bagossi, P., Cheng, Y. S., Oroszlan, S., and Tozser, J. (1996). Activity of linked HIV-1 proteinase dimers containing mutations in the active site region. Protein Eng 9, 997-1003.
1993
Weber, I. T., Tozser, J., Wu, J., Friedman, D., and Oroszlan, S. (1993). Molecular model of equine infectious anemia virus proteinase and kinetic measurements for peptide substrates with single amino acid substitutions. Biochemistry 32, 3354-3362.
Tozser, J., Friedman, D., Weber, I. T., Blaha, I., and Oroszlan, S. (1993). Studies on the substrate specificity of the proteinase of equine infectious anemia virus using oligopeptide substrates. Biochemistry 32, 3347-3353.
1992
Tozser, J., Weber, I. T., Gustchina, A., Blaha, I., Copeland, T. D., Louis, J. M., and Oroszlan, S. (1992). Kinetic and modeling studies of S3-S3' subsites of HIV proteinases. Biochemistry 31, 4793-4800.
Blaha, I., Tozser, J., Kim, Y., Copeland, T. D., and Oroszlan, S. (1992). Solid phase synthesis of the proteinase of bovine leukemia virus. Comparison of its specificity to that of HIV-2 proteinase. FEBS Lett 309, 389-393.
1991
Tozser, J., Gustchina, A., Weber, I. T., Blaha, I., Wondrak, E. M., and Oroszlan, S. (1991). Studies on the role of the S4 substrate binding site of HIV proteinases. FEBS Lett 279, 356-360.
Tozser, J., Blaha, I., Copeland, T. D., Wondrak, E. M., and Oroszlan, S. (1991). Comparison of the HIV-1 and HIV-2 proteinases using oligopeptide substrates representing cleavage sites in Gag and Gag-Pol polyproteins. FEBS Lett 281, 77-80.
Tozser, J., and Berta, A. (1991). Plasminogen activator inhibitors in human tears. Acta Ophthalmol (Copenh) 69, 426-431.
Blaha, I., Nemec, J., Tozser, J., and Oroszlan, S. (1991). Synthesis of homologous peptides using fragment condensation: analogs of an HIV proteinase substrate. Int J Pept Protein Res 38, 453-458.
Berta, A., Holly, F. J., Tozser, J., and Holly, T. F. (1991). Tear plasminogen activators--indicators of epithelial cell destruction. The effect of scraping, n-heptanol debridement, and alkali burn of the cornea on the plasminogen activator activity of rabbit tears. Int Ophthalmol 15, 363-369.
1990
Tozser, J., Marsalko, T. M., Punyiczki, M., and Elodi, P. (1990). The enzyme capable to cleave trypsin active site titrant as substrate is a carboxylesterase with electrophoretic mobility similar to albumin. Acta Biochim Biophys Hung 25, 57-65.
Tozser, J., and Berta, A. (1990). Urokinase-type plasminogen activator in rabbit tears. Comparison with human tears. Exp Eye Res 51, 33-37.
Copeland, T. D., Wondrak, E. M., Tozser, J., Roberts, M. M., and Oroszlan, S. (1990). Substitution of proline with pipecolic acid at the scissile bond converts a peptide substrate of HIV proteinase into a selective inhibitor. Biochem Biophys Res Commun 169, 310-314.
Berta, A., Tozser, J., and Holly, F. J. (1990). Determination of plasminogen activator activities in normal and pathological human tears. The significance of tear plasminogen activators in the inflammatory and traumatic lesions of the cornea and the conjunctiva. Acta Ophthalmol (Copenh) 68, 508-514.
1989
Tozser, J., Hamvas, A., Rady, P., Kertai, P., and Elodi, P. (1989). Plasminogen activator and plasmin-like activities in experimental rat tumours. Acta Biochim Biophys Hung 24, 119-128.
Tozser, J., Berta, A., and Punyiczki, M. (1989). Plasminogen activator activity and plasminogen independent amidolytic activity in tear fluid from healthy persons and patients with anterior segment inflammation. Clin Chim Acta 183, 323-331.
Berta, A., Vamosi, P., and Tozser, J. (1989). [A new method for semi-quantitative alpha 1-antitrypsin determination in human tear fluid]. Fortschr Ophthalmol 86, 773-776.
1986
Tozser, J., Szabo, G., Pozsgay, M., Aurell, L., and Elodi, P. (1986). Active centre studies on bovine pancreatic chymotrypsin with tripeptidyl-p-nitroanilide substrates. Acta Biochim Biophys Hung 21, 335-348.
Szabo, G., Tozser, J., Aurell, L., and Elodi, P. (1986). Mapping of the substrate binding site of human leukocyte chymotrypsin (cathepsin G) using tripeptidyl-p-nitroanilide substrates. Acta Biochim Biophys Hung 21, 349-362.