Vol. 10 Supplement 2 2005

IPK'2005

4th International Conference on Inhibitors of Protein Kinases

and

Workshop on Modelling of Specific Molecular Recognition Processes

June 25 - 29, 2005, Warsaw, Poland

DESIGN * STRUCTURAL BIOLOGY * PHOSPHORYLATION/ DEPHOSPHORYLATION MECHANISMS * SIGNALING PATHWAYS * BIOCHEMISTRY * BIOTECHNOLOGY * CLINICAL ASPECTS * CHEMOTHERAPY

Volume 10 (2005) pp 9
Title PREFACE
Authors David Shugar
  This special issue of Cellular & Molecular Biology Letters presents the Abstracts of Invited Lectures, and of submitted accepted posters (several of which have been selected for short oral presentation) to the 4th International Conference on INHIBITORS OF PROTEIN KINASES (IPK'2005), to take place in Warsaw, Poland, June 25-29, 2005. Also included are Abstracts of several invited lectures, and submitted posters, at an associated Workshop on "Modelling of Specific Molecular Recognition Processes", and relevance to protein kinases. Protein phosphorylation is widely recognized as the most important pathway for regulation of protein functions in living cells, by switching cellular activities from one state to another and, in this way, regulating gene expression, cell proliferation and differentiation. It is the major mechanism whereby cells respond to extracellular signals, such as hormones and growth factors, thus controlling all events at various stages of the cell cycle, as well as the response of the cell to environmental and nutritional stress. Reversible protein phosphorylation is catalyzed by the interplay between protein kinases and protein phosphatases. Given the key role of protein kinases in signal transduction, it was to be anticipated that this would stimulate searches for inhibitors. But, in striking contrast to other enzyme systems, more than 500 protein kinases have now been identified in the human genome alone, all of them catalyzing a similar reaction. It would therefore appear to be a formidable task to develop potent, selective, and cell-permeable, inhibitors for a given kinase. However, a variety of sophisticated approaches, both experimental and theoretical, directed towards this goal have resulted in remarkable progress, as will be seen from the Abstracts in a session on this subject. Notwithstanding the fact that most of them are ATPcompetitive, it is clear that subtle differences in the unique conformations of the catalytic pockets (conformational flexibility, induced fit) play a key role in determining selectivity. Many relatively selective inhibitors are now routinely employed in experiments designed to delineate signal transduction pathways. In this context, it is worth noting, as pointed out recently by Doriano Fabbro of Novartis [Assays & Drug Develop. Technol. 2 (2004) 2-6], that "availability of a good lead (compound) is the key to successful optimization and is much more important than the availability of a structure of the target". This is in line with our own experience in the initial development of tetrabromo- benzotriazole and benzimidazole selective cell-permeable inhibitors of protein kinase CK2 from various sources. But, once a good lead compound has been identified, by whatever means, subsequent structure-based design for further optimization has decisively demonstrated its merits. Furthermore, it has long been known that dysfunctions in activities of protein kinases (and phosphatases) may lead to severe pathological states. It is consequently not surprising that the Biotechnology sector, frequently in collaboration with Academia, is presently devoting major efforts (30 - 40% of their research budgets) to "targeting" protein kinases for drug development, with considerable achievements to date, Gleevec being a prime, but by no means the only, example. It is, consequently, most appropriate that, as at previous IPK meetings, participants at the present Conference include representatives of some major Biotechnology firms actively engaged in this field. A novel feature of the 3rd International Conference (IPK'2003) was a special session on the newly emerging field of protein kinases of pathogenic agents such as viruses, parasites and fungi. Bearing in mind current world-wide efforts to cope with diseases such as malaria (which alone is responsible for more than 1 million deaths annually), caused by protozoan parasites, the present Conference includes a special session on the protein kinases of parasitic protozoa, as well as of their host cells, and accompanying efforts to develop inhibitors of these enzymes as therapeutic agents. Another field that is slowly coming to the forefront is that of histidine kinases of the two-component type, hitherto well characterized in bacteria, plants and fungi. There is now compelling evidence for such enzymes in mammalian cells, and two speakers at this meeting will present up-to-date reviews on what is known about histidine kinases and histidine phosphatases in mammalian systems. We wish to express our appreciation to members of the International Advisory Board for assistance in organizing the program and, in particular, to Christian Doerig and Laurent Meijer for their help in preparing the sessions on parasite kinases and selective kinase inhibitors, respectively. We are indebted to most of the contributors to this Conference, who have complied with our request for Abstracts that are informative, including key references; and to Barbara Kleyny of the IPK Secretariat for her unstinting efforts in checking their conformity with the requirements of the journal.
Pdf Document [Rozmiar: 1332 bajtów]

Volume 10 (2005) pp 11-91
Invited Lectures
Abstracts List CONTROLLING SUBSTRATE SPECIFICITY IN PROTEIN KINASES THROUGH CHEMICAL CLAMPING
Joseph A. Adams - p13

MAMMALIAN HISTIDINE KINASES
Paul V. Attwood and Paul G. Besant - p16

ATP-NONCOMPETITIVE INHIBITORS OF THE C-JUN N-TERMINAL KINASE (JNK) SUBFAMILY - WHAT CAN THEY OFFER?
Marie A. Bogoyevitch and Renae K. Barr - p19

SCREENING ERK2 PROTEIN AND PEPTIDE ASSOCIATIONS BY FLUORESCENCE ANISOTROPY: INSIGHTS INTO ERK2 FUNCTION AND REGULATION BY PROTEIN-PROTEIN INTERACTIONS
Kari Callaway, Mark Rainey and Kevin N. Dalby - p22

ANALYSIS AND CHARACTERISATION OF PROTEIN KINASE INHIBITOR SELECTIVITY AND FUNCTION
Henrik Daub - p25

REGULATORY FUNCTIONS OF SERYL-PHOPHORYLATED HPr IN PATHOGENIC BACTERIA
Josef Deutscher, Rana Herro and Sandrine Poncet - p28

PROTEIN KINASES OF PARASITIC PROTOZOA AND THEIR HOST CELLS: TARGETS FOR CHEMOTHERAPEUTIC INTERVENTION?
Christian Doerig - p30

THE P. falciparum CDK FAMILY: STRUCTURAL STUDIES AND IMPLICATIONS FOR INHIBITOR DESIGN
Anais Merckx, Alex Zawaira, Simon Holton, Christian Doerig, Martin Noble and Jane Endicott - p33

DOMAIN TRUNCATION, POINT MUTATION, AND SURROGATION FOR STRUCTURE BASED KINASE INHIBITOR DESIGN
Christine B. Breitenlechner, Robert Huber, Dirk Bossemeyer, Michael Gassel, Birgit Masjost and Richard A. Engh - p35

TARGETING MALARIA WITH SPECIFIC CDK INHIBITORS
Jeanne A. Geyer, April K. Kathcart, Apurba K. Bhattacharjee, Yueqin Chen, Edison A. Cortes, Sean T. Prigge and Norman C. Waters - p38

MANIPULATION OF ALTERNATIVE SPLICING BY SPECIFIC INHIBITORS OF SR PROTEIN KINASES
Masatoshi Hagiwara - p40

BAKER'S YEAST AS A TOOL FOR THE DEVELOPMENT OF ANTIFUNGAL KINASE INHIBITORS - TARGETING PROTEIN KINASE C AND THE CELL INTEGRITY PATHWAY
Jürgen J. Heinisch - p42

IMMUNOSUPPRESSANTS AS NOVEL ANTI-INFLAMMATORY DRUGS AFFECTING MAPK SIGNALLING PATHWAYS
Bożena Kamiłska - p45

DIACYLGLYCEROL SIGNALING: TARGETING PROTEIN KINASE C ISOZYMES AND "NON-KINASE" DIACYLGLYCEROL EFFECTORS
Marcelo G. Kazanietz - p47

SCANNING THE PROTEOME FOR TARGETS OF KINASE INHIBITORS USING BI-FUNCTIONAL RECEPTOR LIGANDS
Nikolai Kley - p50

REVERSIBLE PHOSPHORYLATION OF HISTIDINE RESIDUES IN VERTEBRATE PROTEINS
Susanne Klumpp, Anette Maeurer, Thomas Wieland and Josef Krieglstein - p52

PREDICTION OF SUBSTRATE SPECIFICITIES OF PROTEIN KINASES
Boštjan Kobe and Ross I. Brinkworth - p54

THE RIO KINASES: STRUCTURAL STUDIES OF A FAMILY OF ATYPICAL PROTEIN KINASES REQUIRED FOR RIBOSOME BIOGENESIS AND CELL CYCLE PROGRESSION
Nicole LaRonde-LeBlanc and Alexander Wlodawer - p57

SIGNALING PROTEIN INHIBITORS via THE COMBINATORIAL MODIFICATION OF PEPTIDE SCAFFOLDS
David S. Lawrence - p60

ADVANCES IN THE STRUCTURAL BIOLOGY, DESIGN AND CLINICAL DEVELOPMENT OF BCR-ABL KINASE INHIBITORS FOR THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA
Paul W. Manley, Sandra Cowan-Jacob and Jürgen Mestan - p62

THE SELECTIVITY OF PHARMACOLOGICAL INHIBITORS OF CYCLIN-DEPENDENT KINASES (CDKS) AND GLYCOGEN SYNTHASE KINASE -3 (GSK-3)
Laurent Meijer - p66

PROTEIN KINASES OF TRYPANOSOMATIDS AS DRUG TARGETS
Jeremy C. Mottram, Christina Naula, Tansy Hammarton and Marilyn Parsons - p69

DESIGNING SPECIFIC INHIBITORS OF THE BACTERIAL HPr KINASE / PHOSPHORYLASE
Sylvie Nessler - p71

EXPLOITING STRUCTURAL PRINCIPLES TO GENERATE PROTEIN KINASE INHIBITORS
Martin Noble, Paul Barrett, Jane Endicott, Louise Johnson, Jim Mcdonnell, David Pratt and Giles Robertson - p74

THE ROLE OF SMG-1, A MEMBER OF THE PIKK (PHOSPHOINOSITIDE 3-KINASE RELATED KINASES ) FAMILY, IN mRNA SURVEILLANCE; MOLECULAR MECHANISM AND THERAPEUTIC IMPLICATIONS
Shigeo Ohno - p76

FEATURES AND POTENTIALS OF ATP-SITE DIRECTED CK2 INHIBITORS
Lorenzo A. Pinna - p78

PROTEIN KINASE STRUCTURE AND FUNCTION ANALYSIS WITH CHEMICAL TOOLS
Kui Shen, Aliya C. Hines, Dirk Schwarzer, Kerri P. Paumi and Philip A. Cole - p81

DEVELOPMENT OF SPECIFIC RHO-KINASE INHIBITOR AND ITS CLINICAL APPLICATION
Masahiro Tamura and Hiroyoshi Hidaka - p83

DYNAMICS OF SIGNALING BY PKA
Susan S. Taylor, Dominico Vigil, Donald Blumenthal, Jill Trewhella, Choel Kim, Ganesh Anand, David Johnson and Jie Yang - p85

INVOLVEMENT OF THE SMALL PROTEIN TYROSINE PHOSPHATASES TC-PTP AND PTP1B SIGNAL TRANSDUCTION IN DISEASES; FROM DIABETES, OBESITY TO CELL CYCLE AND CANCER
Michel L. Tremblay - p88

DISSECTING THE FUNCTIONS OF PROTEIN TYROSINE PHOSPHATASES USING CHEMICAL APPROACHES
Zhong-Yin Zhang - p89


  [Rozmiar: 1332 bajtów]
Posters
Abstracts List MECHANISM OF INHIBITION OF THE PROTEIN KINASE C BY NONSTRUCTURE PROTEIN 3 OF HEPATITIS C VIRUS
Philip Hartjen, Michael Reinholz, Andrea Baier and Peter Borowski - p95

DEPENDENCE OF AMINOGLYCOSIDE 3’-PHOSPHOTRANSFERASE VIII ACTIVITY AND ANTIBIOTIC RESISTANCE ON Ca2+-DEPENDENT PROTEIN SERINE/THREONINE KINASES IN ACTINOMYCETES
Valery N. Danilenko, Sergei M. Elizarov and Maria G. Alekseeva - p97

ORALLY-ACTIVE PYRIDOPYRIMDINE INHIBITORS OF TRANSFORMING GROWTH FACTOR BETA RI (ALK5) KINASE. STRUCTURE AND ACTIVITY, in-vitro AND in-vivo CHARACTERIZATION
Sarvajit Chakravarty and Sundeep Dugar - p99

ISOFLAVONOIDS AND THEIR 3' AND 4'-O-SUBSTITUED DERIVATIVES AS INHIBITORS OF SH2 DOMAIN OF p56lck PROTEIN TYROSINE KINASE
Agnieszka Godlewska, Rafał Augustyniak and Paweł Bodera - p100

EVALUATION OF 3-CARBOXY-4-(1H)-QUINOLONES AS INHIBITORS OF HUMAN PROTEIN CASEIN KINASE 2
Andriy G. Golub, Volodymyr G. Bdzhola, Olexander Ya. Yakovenko, Vladislav M. Sapelkin and Sergiy M. Yarmoluk - p102

EFFECT OF TRICHOSTATIN A ON TRANSCRIPTION OF SELECTED SIGNAL MOLECULE GENES IN JURKAT T CELLS
Radosław Januchowski and Paweł P. Jagodziłski - p103

mTOR AND p70S6K PHOSPHORYLATION BY INSULIN ± RAPAMYCIN IN HepG2 CELLS WITH AND WITHOUT OVEREXPRESSION OF CONSTITUTIVELY ACTIVE Akt/PKB
Shailly Varma, Dhanajay Gupta and Ramji L. Khandelwal - p105

SEARCHING FOR INHIBITORS OF CDPK AS POTENTIAL DRUGS AGAINST PARASITES?
Maria Klimecka, Jadwiga Szczegielniak, Luiza Koper, Marcin KoÂśliłski and Grażyna Muszyłska - p107

INSULIN-LIKE GROWTH FACTOR-1 INITIATES A NEGATIVE FEED BACK MECHANISM BY JNK ACTIVATED SHP1 TO REGULATE PROLIFERATION OF BREAST CANCER CELLS
Shahreen Amin, Ashok Kumar, Joan Lee and Maya Kozlowski - p108

MOLECULAR DYNAMICS STUDY OF PROTEIN-LIGAND INTERACTIONS
Zdeněk Kříž, Michal Otyepka, Iveta Bártová and Jaroslav Koča - p111

CYCLIN-DEPENDENT KINASE INHIBITOR OLOMOUCINE II INTERACTS WITH CDK2 AND CDK9
Vladimír Kryštof, Martin Orság, Martina Paprskářová, Petr Müller, Bořivoj Vojtěšek and Miroslav Strnad - p113

MOLECULAR DYNAMICS SIMULATIONS OF PHOSPHOLAMBAN: EFFECTS OF MEMBRANE, PHOSPHORYLATION AND AGGREGATION
Yao Houndonougbo, Gouri S. Jas and Krzysztof Kuczera - p114

DYNAMICS OF HUMAN CDK2 AND CDK5 STUDIED BY COMPUTER SIMULATIONS
Michal Otyepka, Iveta Bártová, Zdeněk Kříž and Jaroslav Koča - p116

THE INTERACTION BETWEEN PROTEIN KINASE C EPSILON AND FOCAL ADHESION KINASE
Ewa Totoł, Johann Hofmann and Maria Rybczyłska - p118

THE PHYSICAL NATURE OF CAMP-DEPENDENT PROTEIN KINASE CATALYTIC ACTIVITY: AB INITIO DIFFERENTIAL TRANSITION STATE STABILIZATION ANALYSIS OF THE KEY ACTIVE SITE RESIDUES
Paweł Szarek, Edyta Dyguda, W. Andrzej Sokalski, Yuhui Cheng, Yingkai Zhang and J. Andrew McCammon - p119

ASF1 - YEAST INDUCTOR OF APOPTOSIS INHIBITS CK2 ACTIVITY in vitro
Monika Jach, Konrad Kubiński, Rafał Zieliński, Ewa Sajnaga and Ryszard Szyszka - p121

IP6 MODULATES INTERLEUKIN-8 SECRETION IN COLON EPITHELIAL CELLS BY INFLUENCING VARIOUS SIGNALING PATHWAYS
Ludmiła Węglarz, Joanna Wawszczyk, Arkadiusz Orchel and Zofia Dzierżewicz - p124

IMPLEMENTATION OF ORBITAL GRAPH MODEL FOR PARTIAL ATOM CHARGES DEFINITION IN VIRTUAL SCREENING TECHNIQUES
Olexander Ya. Yakovenko, Andriy G. Golub, Volodymyr G. Bdzhola and Sergiy M. Yarmoluk - p126

  [Rozmiar: 1332 bajtów]
Abstracts of posters selected for oral presentation
Abstracts List NAVIGATING CROSS-KINASE SELECTIVITY SPACE
Alex M. Aronov, Brian Mcclain, Paul R. Caron and Mark A. Murcko - p129

MALARIA PARASITE TRANSMISSION TO THE MOSQUITO IS REGULATED BY UNUSUAL PROTEIN KINASES WITH STAGE-SPECIFIC ESSENTIAL FUNCTIONS
Oliver Billker, Christian Doerig, Rita Tewari, Inga Siden-Kiamos, Robert Moon and Dominique Dorin 131

ALK 5 (TGF BETA RI) INHIBITORS: In-vitro AND In-vivo CHARACTERIZATION OF NOVEL ORALLY ACTIVE PTERIDINES
Sarvajit Chakravarty and Sundeep Dugar - p133

A NOVEL NON-CATALYTIC INHIBITORY MECHANISM EMPLOYED BY THE CSK-HOMOLOGOUS KINASE (CHK) TO INACTIVATE SRC-FAMILY PROTEIN KINASES
Heung-Chin Cheng, Yuh-Ping Chong and Terrence Mulhern - p135

CLASSIFICATION AND CHARACTERIZATION OF NATURAL PROTEIN INHIBITORS OF PROTEIN KINASES
Agata Meglicz, Jacek Leluk and Bogdan Lesyng - p137

IMPLICATIONS OF KINASE SIMILARITY IN DRUG DISCOVERY
Michal Vieth and Jeffrey Sutherland - p139

TETRABROMOBENZOTRIAZOLE (TBBt) AND TETRABROMOBENZIMIDA-ZOLE (TBBz): SELECTIVE INHIBITORS OF PROTEIN KINASE CK2, AND THEIR INFLUENCE ON ACTIVITIES OF DIFFERENT FORMS OF HUMAN CK2, AND ON THE CELLS
Piotr Zień, David W. Litchfield, James Duncan, Janusz Skierski, Maria Bretner and David Shugar - p141

  [Rozmiar: 1332 bajtów]
Workshop on modelling of specific molecular recognition processes
Abstracts List ALTERNATIVE BINDING MODES OF PROLINE-RICH PEPTIDES BINDING TO THE GYF DOMAIN
Wei Gu, Michael Kofler, Iris Antes, Christian Freund and Volkhard Helms - p145

TARGET FLEXIBILITY IN MOLECULAR RECOGNITION
J. Andrew McCammon - p146

MULTIPLE MOLECULAR RECOGNITION MECHANISMS. CYTOCHROME P450 - A CASE STUDY
Rebecca C. Wade, Domantas Motiejunas, Karin Schleinkofer, Sudarko, Peter J. Winn and Amit Banerjee - p147

RAPID PROTEIN-LIGAND DOCKING USING SOFT MODES FROM MD SIMULATIONS TO ACCOUNT FOR PROTEIN DEFORMABILITY: APPLICATION TO PROTEIN KINASE-LIGAND INTERACTIONS
Martin Zacharias - p149

  [Rozmiar: 1332 bajtów]