Curriculum Vitae

Dr. Nikos G. Oikonomakos
Director
Tel: + 30 210 7273884
Fax: +30 210 7273831
E-mail: ngo
Personal homepage

Dr. N.G. Oikonomakos is the Director of the Institute of Organic and Pharmaceutical Chemistry (IOPC) of the National Hellenic Research Foundation and Head of the Structural Biology and Chemistry Group (SBCG). Diploma in Chemistry (1970), Doctorate in Chemistry (1977), University of Athens, Greece. Research Fellow in the Laboratory of Molecular Biophysics, University of Oxford, Oxford, UK (1983-1984, 1986-1987, 1994-1995). Main fields of specialization: Structural Biology, Structure-based Drug Design, Protein crystallography, Enzymes, Biochemistry. He has theoretical and practical expertise (over 20 years) in the key enzymes of glycogen metabolism. The elucidation of the catalytic mechanisms of glycogen phosphorylase and phosphorylase kinase is well documented in e.g. Donald Voet & Judith G. Voet Biochemistry (1995) 2 nd ed, John Wiley & Sons, Inc, New York, Lubert Stryer's Biochemistry (1996), Nicholas C. Price & Lewis Stevens Fundamentals of Enzymology, 3 rd ed, Oxford Univ. Press (1999), Alan Fersht Structure and Mechanism in Protein Science, A Guide to Enzyme Catalysis and Protein Folding, W.H. Freeman and Company, New York (1999), David E. Metzler's Biochemistry, The Chemical Reactions of Living Cells, 2 nd ed, Vol.1, Academic Press (2001), Jeremy M. Berg, John L. Tymoczko & Lubert Stryer's Biochemistry, 5 th ed., W.H. Freeman and Company, New York (2002), where the present state of the art is traced back to his achievements together with Prof. Dame L. N. Johnson's group (Univ. of Oxford, Oxford, UK). His current research aims to understand structure and function of (1) proteins involved in the control of glycogen metabolism, (2) calcium/calmodulin regulated kinases, (3) RNases, (4) lectins, (5) nicotinic acetylcholine receptor, (6) phosphoenolpyruvate carboxykinase, (7) glucokinase, (8) TAFs9 proteins, (9) alkaline xylanases F/10, F/11, and (10) esterases A and B of ferulic acid from Fusarium oxysporoum. Registered user (since 1983) of the European Synchrotron Radiation Sources for X-ray crystallographic data collection of the Synchrotron Radiation Source, Daresbury Laboratory, Daresbury, UK, Sinchrotrone Trieste, Trieste, Italy, EMBL, Hamburg-Outstation, DESY, and ESRF, Grenoble, France, through grant applications. He is participating in the European Structural Biology Forum (ESBF), a network aiming to obtain structural data on all known protein families that have been identified through the genome sequencing efforts. More than 100 publications as refereed articles, reviews, and chapters in Books. He has supervised 9 PhD Theses, 4 MSc, and 24 final year projects. Research grants obtained come from national sources (Greek general secretariat for research & technlology), EU (SCIENCE, HUMAN CAPITAL & MOBILITY, BIOMED, BIOTECHNOLOGY, MARIE CURIE, HPRN), Organisations-Universities (Wellcome Trust, Royal Society, Medical Research Council, FEBS, EMBO, University of Dundee) and Pharmaceutical Companies.

Recent publications

Oikonomakos, N.G., Schnier, J.B., Zographos, S.E., Skamnaki, V.T., Tsitsanou, K.E., and Johnson, L.N. (2000). Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site. J. Biol. Chem. 275, 34566-34573.{PDB code: 1C8K}

Oikonomakos, N.G., Skamnaki, V.T., Tsitsanou, K.E., Gavalas, N.G., and Johnson, L.N. (2000). A new allosteric site in glycogen phosphorylase b as a target for drug interactions. Structure 8, 575-584. {PDB code: 1C50}

Kontou, M., Leonidas, D.D., Vatzaki, E.H., Acharya, K.R., Mamalaki, A., Oikonomakos, N.G., and Tzartos, S.J. (2000). The crystal structure of a Fab fragment of a rat monoclonal antibody against the main immunogenic region of the human muscle acetylcholine receptor. Eur. J. Biochem. 267, 2389-2396. {PDB code: 1C5D}

Tsitsanou, K.E., Skamnaki, V.T., and  Oikonomakos, N.G. (2000). Structural basis of the synergistic inhibition of glycogen phosphorylase a by caffeine and a potential antidiabetic drug. Arch. Biochem. Biophys. 384, 245-254.{PDB code: 1C8L}

Skamnaki, V.T., Oikonomakos, N.G. (2000). Kinetic characterization of the double mutant R148A/E182S of glycogen phosphorylase kinase catalytic subunit: the role of the activation loop. J. Protein Chem. 19, 499-505.

Poulas K, Eliopoulos E., Vatzaki E., Navaza J., Kontou M., Oikonomakos N., Acharya K.R., Tzartos S.J. (2001). Crystal structure of Fab198, an efficient protector of the acetylcholine receptor against myasthenogenic antibodies. Eur. J. Biochem., 268, 3685-93. {PDB code: 1FN4}

Oikonomakos, N.G., Skamnaki, V.T., Osz, E., Szilagyi, L., Somsak, L., Docsa, T., Toth, B. and Gergely, P. (2002). Kinetic and crystallographic studies of glucopyranosylidene spirothiohydantoin binding to glycogen phosphorylase b. Bioorg. Med. Chem. 10, 261-268. {PDB code: 1HLF}

Oikonomakos, N.G., Zographos, S.E., Skamnaki, V.T. and Archontis, G. (2002). The 1.76 A resolution crystal structure of glycogen phosphorylase b complexed with glucose, and CP320626, a potential antidiabetic drug. Bioorg. Med. Chem. 10, 1313-1319. {PDB code: 1H5U}

Oikonomakos, N.G., Kosmopoulou, M., Zographos, S.E., Leonidas, D.D., Chrysina, E.D., Somsak, L., Nagy, V., Praly, J.P., Docsa, T., Toth, B. and Gergely, P. (2002). Binding of N-acetyl-N'-beta-D-glucopyranosyl urea and N-benzoyl -N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies. Eur. J. Biochem. 269, 1684-1696. {PDB codes: 1K06, 1K08, 1KTI} Cover Story

Cook, A., Lowe, E.D., Chrysina, E.D., Skamnaki, V.T. Oikonomakos, N.G. and Johnson, L.N. (2002). Structural studies of Phospho-CDK2/Cyclin A bound to nitrate, a transition state analogue: Implications for the protein kinase mechanism. Biochemistry 41, 7301-7311. {PDB code: 1GY3}

Oikonomakos, N.G. (2002). Glycogen phosphorylase as a molecular target for type 2 diabetes therapy. Curr Protein Pept Sci. 3, 561-586. Cover Story

Oikonomakos N.G, Chrysina, E.D., Kosmopoulou, M.N. and Leonidas, D.D. (2003) Crystal structure of rabbit muscle glycogen phosphorylase a in complex with a potential hypoglycaemic drug at 2.0 A resolution. (2003) Biochim. Biophys. Acta 1647, 325-332. {PDB codes: 1LWN, 1LWO}

Leonidas, D.D.,  Swamy, B.M., Bhat, A.G.,  Inamdar, S.R., Kosmopoulou,  M.N., Chrysina, E.D., and Oikonomakos, N.G. (2003) Crystallization and preliminary X-ray crystallographic analysis of Sclerotium rolfssii lectin. Acta Cryst. D59, 363-365.

Chrysina, E.D., Oikonomakos, N.G., Zographos, S.E., Kosmopoulou, M.N., Bischler, N., Leonidas, D.D., Kovacs, L., Docsa, T., Gergely, P., and Somsak L. (2003) Crystallographic studies on alpha- and beta-D-glucopyranosyl formamide analogues, inhibitors of glycogen phosphorylase. Biocatal. & Biotransfor. 21, 233-242. {PDB codes: 1P4G, 1P4H, 1P4J}

Pinotsis, N., Leonidas, D.D., Chrysina, E.D., Oikonomakos, N.G., and Mavridis, I.M. (2003). The binding of beta- and gamma-cyclodextrins to glycogen phosphorylase b: kinetic and crystallographic studies. Protein Sci. 12, 1914-1924.Cover Story {PDB codes: 1P2G, 1P29, 1P2D, 1P2B}

Leonidas, D.D., Chabali, G.B., Chrysina, E.D., Kosmopoulou, M.N., Oikonomakos, N.G., Vlassi, M., Frankling, C. and Acharya, K.R. (2003). High resolution crystal structures of Ribonuclease A complexed with adenylic and uridylic nucleotide inhibitors. Implications for structure-based design of ribonucleolytic inhibitors. Protein Sci. 12, 2559-2574.Cover story {PDB codes: 1O0H, 1O0N, 1O0F, 1O0O}

Kosmopoulou, M.N., Leonidas, D.D., Chrysina, E.D., Bischler, N., Eisenbrand, G., Sakarellos, C.E., Pauptit, R., Oikonomakos, N.G. (2004). Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor site of rabbit muscle glycogen phosphorylase b.Eur. J. Biochem. 271, 2280-2290.{PDB codes: 1UZU)

Chrysina, E.D., Kosmopoulou, M.N., Kardakaris, R., Bischler, N., Leonidas, D.D., Kannan, T., Loganathan, T., and Oikonomakos, N.G. (2005) Binding of b -D-glucopyranosyl bismethoxyphosphoramidate to glycogen phosphorylase b. Kinetic and crystallographic studies. Bioorg. Med. Chem. 13, 765-772. {PDB code: 1XC7}

Chrysina, E.D., Kosmopoulou, M.N., Tiraidis, C., Kardakaris, R., Bischler, N., Leonidas, D.D., Hadady, Z., Somsak, L., Docsa, T., Gergely, P., and Oikonomakos, N.G. (2005). Kinetic and crystallographic studies on 2-( b -D-glucopyranosyl)-5-methyl-1, 3, 4-oxadiazole, -benzothiazole, and -benzimidazole, inhibitors of muscle glycogen phosphorylase b. Evidence for a new binding site. Protein Sci. 14, 873-888. {PDB codes: 1XL0, 1XL1, 1XKX}

Oikonomakos, N.G., Kosmopoulou, M.N., Chrysina, E.D., Leonidas, D.D., Kostas, I.D., Wendt, K.U., Klabunde, T., and Defossa, E. (2005) Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs. Protein Sci., in press. {PDB codes: 1WUT, 1WVX, 1WV0, 1WV1}

Watson, K.A., Chrysina, E.D., Tsitsanou K.E., Zographos, S.E., Gregoriou, M., Archontis, G., Fleet, G.W.J., and Oikonomakos, N.G. (2005) Kinetic and crystallographic studies of glucopyranose spirohydantoin and glucopyranosylamine analogues inhibitors of glycogen phosphorylase. Proteins: Structure, Function, and Bioinformatics, in press. {PDB codes: 1GGN, 1FTQ, 1FTW, 1FTY, 1FU4, 1FU7, 1FU8, 1P4H, 1FS4, 1B4D, 1GG8, 2PRJ}

Archontis, G., Watson, K.A., Xie, Q., Andreou, G., Chrysina, E.D., Zographos, S.E., Oikonomakos, N.G., and Karplus, M. (2005) Molecular recognition and relative binding of glucopyranose spirohydantoin analogues to glycogen phosphorylase: a free energy perturbation study. Proteins: Structure, Function, and Bioinformatics, in press.

Hatzopoulos, G.N., Leonidas, D.D., Kardakaris, R., Kobe, J., and Oikonomakos, N.G. (2005) The binding of IMP to ribonuclease A. FEBS Journal, in press.

Kosmopoulou, M.N., Leonidas, D.D., Chrysina, E.D., Eisenbrand, G., and Oikonomakos, N.G. (2005) Indirubin-3'-aminooxy-acetate inhibits glycogen phosphorylase by binding at the inhibitor and the allosteric site. Broad specificities of the two sites. Letters in Drug Design & Discovery, in press. {PDB code: 1Z62}

Klabunde, T., Wendt, K.U., Kadereit, D., Brachvogel, V., Burger, H.-J., Herling, A.W., Oikonomakos, N.G., Kosmopoulou, M.N., Schmoll, D., Sarubbi, E., von Roedern, E., Schonafinger, K., and Defossa, E. (2005). Acyl Ureas as Human Liver Glycogen Phosphorylase Inhibitors for the Treatment of Type 2 Diabetes. J. Med. Chem., in press.