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Michael Karpusas, Ph.D

Associate Professor of Biophysics

Laboratory of Physics, Department of Biotechnology
Agricultural University of Athens
Iera Odos 75 , Athens 11855, Greece

TEL: 30-210-5294221
FAX: 30-210-5294233

E-mail: mkarp@aua.gr

EDUCATION:

Ph.D, Biophysics, 1990, University of Oregon

M.Sc., Biophysics, 1989, University of Oregon

B.Sc, Physics (with distinction), 1985, University of Thessaloniki

RESEARCH INTERESTS:

Protein crystallography, structural biology, structure-based drug design.

PUBLICATIONS:

1. Karpusas, M., Baase, W., Matsamura, M. and Matthews, B.W.," Hydrophobic packing in T4 lysozyme probed by cavity-filling mutants." (1989) Pro.Nat.Acad.Sci.(USA) 86, 8237-8241

2. Karpusas, M., Branchaud, B. and Remington S.J.: " Proposed Mechanism for the condensation reaction of citrate synthase: 1.9 Å structure of the ternary complex with oxaloacetate and carboxymethyl Coenzyme A" (1990) Biochemistry 29, 2213-2219

3. Karpusas, M., Holland, D. and Remington, S.J.: " 1.9 Å structures of ternary complexes of citrate syntase with D- and L-malate: Mechanistic implications"(1991) Biochemistry 30, 6024-6031

4. Liao, D-I, Karpusas, M. and Remington, S.J.: "Crystal structure of an open conformation of citrate synthase from chicken heart at 2.8 Å resolution." (1991) Biochemistry 30, 6031-6036

5. Wang, J., Pepinski, B., Karpusas, M, Liu, J. and Osborn, L.: “Crystallization and preliminary crystallographic analysis of the N-terminal two domain fragment of Vascular Cell Adhesion Molecule-1 (VCAM-1)” (1994) PROTEINS 20, 287-290

6. Osborn, L., Day, E.S, Miller, G.T., Karpusas, M., Tizard, R., Meuer, S.C. and Hochman. P.S. “Amino acid residues required for binding of LFA-3 (CD58) to its counter-receptor CD2.”(1995) J.Exp.Med.181, 429-434

7. Collins, E.J., Garboczi, D., Karpusas, M. and Wiley, D.C. “The three-dimensional structure of a Class I MHC molecule missing the a3 domain of the heavy chain” (1995) Pro.Nat.Acad.Sci.(USA) 92,1218-1221.

8. Wang, J., Pepinsky, R.B, Stehle, T., Liu, J.,Karpusas, M., Browning, B. and Osborn, L. “The crystal structure of an N-terminal two-domain fragment of vascular cell adhesion molecule 1 (VCAM-1): A cyclic peptide based on the domain 1 C-D loop can inhibit VCAM-1-a4 integrin interaction.” (1995) Pro.Nat.Acad.Sci.(USA) 92, 5714-5718.

9. Karpusas, M., Hsu, Y-M., Wang, J.,Thompson, J., Lederman, S., Chess, L. and Thomas, D. “2 Å crystal structure of an extracellular fragment of human CD40 Ligand” (1995) Structure 3, 1031-1039.

10. Lederman, S., Cleary, A. M., Yellin, M.J., Frank, D.M., Karpusas, M., Thomas, D.W. & Chess, L.”The central role of the CD40 ligand and CD40 pathway in T lymphocyte-mediated differentiation of B lymphocytes” (1996) Curr. Opin. in Hematology 3, 77-86

11. Wang, J., Stehle, T.,Pepinsky, R.B, Liu, J., Karpusas, M.,and Osborn, L. “The crystal
structure of a functional fragment of VCAM-1 at 1.9 Å resolution: Implications for integrin and virus binding” (1996) Acta Cryst.D52, 369-379.

12. Karpusas, M., Nolte,M., Benton,C., Meier,W., Lipscomb,W.and Goelz,S. “The crystal structure of human interferon-b at 2.2 Å resolution” (1997) Pro.Nat.Acad.Sci.(USA) 94,
11813-11818.

13. Runkel L., Meier, W., Pepinski, B., Karpusas, M., Kimball, K., Brickelmaier, M., Jones, W. & Goelz,S. "Structural and functional differences between glycosylated and non-glycosylated forms of human interferon-b (IFN-b)" (1998) Pharm Res. 15(4): 641-649.

14. Singh, J., Garber, E., van Vlijmen, H., Karpusas, M., Hsu, Y-M, Zheng, Z., Naismith,J. & Thomas, D. " The role of polar interactions in the molecular recognition of CD40L with its receptor CD40" (1998) Protein Science 7: 1124 -1135.

15. Karpusas, M. , Whitty, A., Runkel, L. & Hochmann, P."The structure of human interferon-b: implications for activity" (1998) Cellular & Mol. Life Sci. 54:1203-1216

16. Taylor, F., Bixler, S., Budman, J., Karpusas, M., Ryan, S., Jaworski, G., Wen, D., Safari-Fard, A., Pollard, S. & Whitty, A." Induced fit activation mechanism of the exceptionally specific serine protease, complement factor D" (1999) Biochemistry 38: 2849-2859

17. Webster, E., Khakoo, A., Yellin, M., Karpusas, M., Thomas, D., Davidson, A., Christian, C. & Lederman, S. "An agressive form of polyarticular arthritis in a man with CD154 mutation (X-linked Hyper-IgM syndrome)" (1999) Arthritis Reum.42(6):1291-6

18. Nolte, M., Pepinski, R.B., Venyaminov, S.Y., Kotelianski, V., Gotwals, P.J. & Karpusas, M." Crystal structure of the a1b1 integrin I-domain: insights into integrin I-domain function" (1999) FEBS Letters 452, 379-385.

19. Garber, E., Su, L., Ehrenfels, B., Karpusas, M. & Hsu, Y-M. “CD154 variants associated with Hyper-IgM syndrome can form oligomers and trigger CD40-mediated signals” (1999) J.Biol.Chem. 274, 33545-33550

20. Runkel, L., deBios, C., Karpusas, M., Betzenhauser, M., Muldowney, C., Zafari, M., Benjamin, C., Miller, S., Hochman, P. & Whitty, A. "Systematic mutational mapping of sites on human interferon-beta-1a that are important for receptor binding and functional activity”(2000) Biochemistry 39, 2538-2551

21. Karpusas, M., Lucci, J., Ferrant,J., Benjamin, C., Taylor, F., Strauch, K., Garber, E., Hsu, Y-M. “Structure of CD40 Ligand in complex with the Fab fragment of a neutralizing humanized antibody” (2001) Structure 9, 321-329

22. Runkel, L., deDios, C., Karpusas, M, Baker, D., Li, Z., Zafari, M., Betzenhauser, M.,
Muldowney, C, Miller, S., Redlich, P.N., Grossberg, SE., Whitty, A., and Hochman, P. “Mapping of Interferon-b Epitopes Important for Receptor Binding and Activation: Comparison of Results Achieved using Antibody-based Methods and Alanine Substitution Mutagenesis” (2001) J. Interferon Cyt. Res . 21, 931-941

23. Karpusas, M., Cachero, TG, Qian, F., Boriack-Sjodin, A., Mullen, C., Strauch, K., Kalled, S.L “Crystal structure of human BAFF, a TNF family member that stimulates B lymphocytes” (2002) J.Mol.Biol. 315, 1145-1154

24. Ferrant, J.L., Wilson, C.A,.Benjamin, C.D., Hess, D.M., Hsu, Y-M, Karpusas, M., Roux, K.H., Taylor, F.R. “ Variation in ordered structure of complexes between CD154 and anti-CD154 monoclonal antibodies” (2002) Mol.Immunol. 39 (1-2): 77-84

25. Singh. J., van Vlijmen, H., Lee, W-C., Liao, Y., Lin,K-C., Ateeq, H., Cuervo, J.,
Zimmerman, C., Hammond, C., Karpusas, M., Palmer, R., Chattopadhyay, T., Adams,S.P. “3D QSAR (COMFA) of a series of potent and highly selective VLA-4 antagonists” (2002) J. Comp.Aid.Mol.Design 16(3): 201-11

26. Zaganas I., Spanaki C., Karpusas M., Plaitakis A.” Substitution of Ser for Arg-443 in the Regulatory Domain of Human Housekeeping (GLUD1) Glutamate Dehydrogenase Virtually Abolishes Basal Activity and Markedly Alters the Activation of the Enzyme by ADP and L-Leucine.” (2002) J.Biol.Chem. 277(48):46552-46558

27. Karpusas, M., Ferrant,J., Weinreb, P., Taylor,F., Garber, E. “Crystal structure of the a1b1 integrin I domain in complex with the Fab fragment of a neutralizing antibody” (2003) J.Mol.Biol. 327, 1031-1041

28. Bukhtiyarova, M., Northrop, K., Chai, X., Karpusas, M., Casper, D. and Springman, E. “Improved expression, purification and crystallization of p38a MAP kinase” (2004) Prot.Exp.Pur. 37(1):154-61

29. Michelotti, E., Moffett, K., Nguyen,D., Kelly, M., Shetty, R., Chai, X., Northrop, K. Namboodiri, V., Flynn, G., Fujimoto, T., Hollinger, F., Bukhtiyarova, M., Springman, E. and Karpusas, M. ”Two classes of p38a MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes” (2005) Biorg.Med.Chem.Lett. 15(23), 5274-5279

30. Bukhtiyarova, M., Karpusas, M., Northrop, K., Namboodiri, H. and Springman, E. ”Mutagenesis of p38a MAP kinase establishes key roles of Phe169 in function and structural dynamics and reveals a novel DFG-out state.” (2007) Biochemistry 46(19), 5687-5696

31. Braoudaki M., Karpusas, M, Katsibardi K, Papathanassiou Ch, Karamolegou K, and Tzortzatou-Stathopoulou F. “Frequency of FLT3 mutations in childhood acute lymphoblastic leukemia” (2008) Mol. Oncology (e-pub Dec 16)

32. Papakyriakou, A., Vourloumis, D., Tzortzatou- Stathopoulou, F. and Karpusas. M. “Conformational dynamics of the EGFR kinase domain reveals structural features involved in activation” (2008) Proteins (e-pub Dec 23)

33. Lamprou, G., Vlahopoulos, S., Papathanassiou, C., Papanikolaou, M., Karpusas, M., Zoumakis, E. and Tzortzatou- Stathopoulou, F. “Prednisolone exerts late mitogenic and biphasic effects on resistant acute lymphoblastic leukemia cells” (2009) Leuk. Res. 33(12): 1684-95

34. Papakyriakou A, Katsarou ME, Belimezi M, Karpusas, M, Vourloumis D. “Discovery of potent vascular endothelial growth factor receptor-2 inhibitors” (2010) ChemMedChem. 5(1):118-29

35. Namboodiri HV, Bukhtiyarova M, Ramcharan J, Karpusas, M, Lee Y, Springman EB. “Analysis of Imatinib and Sorafenib binding to p38alpha compared with c-Abl and b-Raf provides structural insights for understanding the selectivity of inhibitors targeting the DFG-Out Form of protein kinases” (2010) Biochemistry. May 4;49(17):3611-8

36. Kokkinou A, Tsorteki F, Karpusas M, Papakyriakou A, Bethanis K, Mentzafos D. "Study of the inclusion of the (R)- and (S)-camphor enantiomers in alpha-cyclodextrin by X-ray crystallography and molecular dynamics. (2010) Carbohydr Res. May 27;345(8):1034-40

37. Hatziagapiou K., Braoudaki M., Karpusas M., Tzortzatou- Stathopoulou, F. “Evaluation of antitumor activity of gefitinib in pediatric glioblastoma and neuroblastoma cells” (2011) Clinic. Lab. 57(9-10):781-4.

38. Moffett K, Konteatis Z, Nguyen D, Shetty R, Ludington J, Fujimoto T, Lee KJ, Chai X, Namboodiri H, Karpusas M, Dorsey B, Guarnieri F, Bukhtiyarova M, Springman E, Michelotti E. "Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)" (2011) Bioorg Med Chem Lett. 21(23):7155-65.

39. Christoforides, E., Dimou, M. , Katinakis, P., Bethanis, K. and Karpusas, M."Crystal Structure of a Bacterial Cytoplasmic Cyclophilin A in Complex with a Tetrapeptide"(2012) Acta Cryst Sect. F, 68(Pt 3):259-64.

40. Karpusas, M., Axarli, I., Chiniadis, L., Papakyriakou, T., Bethanis K., Scopelitou, K.,. Clonis , YD. and Labrou, NE."The interaction of the chemotherapeutic drug chlorambucil with human glutathione transferase A1-1: kinetic and structural analysis" (2013) Plos One 8(2):e56337

41. Katsimpouras C, Bénarouche A, Navarro D, Karpusas M, Dimarogona M, Berrin JG, Christakopoulos P, Topakas E. Enzymatic synthesis of model substrates recognized by glucuronoyl esterases from Podospora anserina and Myceliophthora thermophila. Appl Microbiol Biotechnol. 2014 Feb 16. [Epub ahead of print]

BOOK CHAPTERS:

Β1. Wozniac, J., Zhang, X-J., Wilson, K., Weaver, L.H., Tronrud, D.E., Pjura, P.E, Nicholson, H., Matsamura, M., Karpusas, M., Jacobson, R., Faber, R., Dao-pin, S., Bell, J.A, Alber, T. and Matthews, B.W, "Crystallographic and Genetic Aproaches toward the design of proteins of enhanced thermostability" in Crystallographic and Modelling Methods in Molecular Design. C.Bugg &S.E.Ealick, eds. Springer-Verlag,New York.

Β2. Bell, J.A, Daopin, S., Faber, R., Jacobson, R., Karpusas, M., Matsamura, M., Nicholson, H., Pjura, P.E, Tronrud, D.E, Weaver, L.H, Wilson, K.P, Wozniac, J.A, Zhang, X-J, Alber,T. and Matthews,B.W. : " Approaches toward the design of proteins of enhanced thermostability" in The use of X-ray crystallography in the design of antiviral agents. Copyright 1990 by Acad. Press.

Β3. Bell, J.A, Brennan, R.G., Daopin, S., Faber, R., Jacobson, R., Karpusas, M., Matsamura, M., Nicholson, H., Pjura, P.E, Roderick, S.L., Tronrud, D.E, Weaver, L.H, Wilson, K.P, Wozniac, J.A, Zhang, X-J and Matthews,B.W. : " Structural and genetic analysis of protein-protein and protein-DNA interactions" in Frontiers in drug research. Alfred Benzon Symposium 28, 281-284 (1990).

Β4. Whitty, A & Karpusas, M. “Structure and activity of human Interferon-b-1a (AVONEX®): A case study of the use of structural data in the arena of protein pharmaceuticals” (2003) Protein Structure Copyright Dekker book publishers