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15th International Symposium on Cytochrome P450. Highlights of the meeting. International Symposia on Cytochrome P450. Year Place Lead organizer 1976 Primosten, Yugoslavia Sinisa Maricic (Klaus Ruckpaul)
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15th International Symposium on Cytochrome P450 Highlights of the meeting
International Symposia on Cytochrome P450 Year Place Lead organizer 1976 Primosten, Yugoslavia Sinisa Maricic (Klaus Ruckpaul) 1978 Eberswalde, GDR Klaus Ruckpaul 1980 Saltsjöbaden, Sweden Jan-Åke Gustafsson 1982 Kuopio, Finland Osmo Hänninen 1985 Budapest, Hungary Laszlo Vereczkey 1988 Vienna, Austria Inge Schuster 1991 Moscow, Russia Alexander Archakov 1993 Lisbon, Portugal Maria C. Lechner 1995 Zürich, Switzerland Wolf Woggon 1997 San Francisco, USA John Dawson 1999 Sendai, Japan Yoshiaki Fujii-Kuriyama & Yuzuru Ishimura 2001 La Grande Motte, France Reinhard Lange 2003 Prague, Czech Republic Pavel Anzenbacher 2005 Dallas, USA Julian Peterson & Sandra Graham 2007 Bled, Slovenia Damjana Rozman 2009 Bankoku Shinmryokan, Japan Hirofumi Shoun 2011 Manchester, UK Andrew Munro
List of sessions Functional genomics P450s and nanotechnology P450 structure and function Transcriptional regulation Heme thiolate proteins P450s in metabolism and drug discovery New mechanisms of P450 reaction P450 cross talks and interactions Post-transcriptional events Biophysical methods Biotechnology and bioinformatics Novel P450-partner interactions
List of sessions Functional genomics P450s and nanotechnology P450 structure and function Transcriptional regulation Heme thiolate proteins P450s in metabolism and drug discovery New mechanisms of P450 reaction P450 cross talks and interactions Post-transcriptional events Biophysical methods Biotechnology and bioinformatics Novel P450-partner interactions
What was new in Bled 2007? 1) Many P450 structures: flexibility/adaptation to different ligands (SF-1 also flexible) Sheds new light on biophysical methods like ITC, RR, high pressure Be cautious when applying radiation on redox proteins 2) Nanobiotechnological approaches: nanodiscs to P450 music 3) Complicated kinetic in some P450 systems 4) New reaction types 5) The first P450 with 2 independent active sites and two reactions catalysed
6) Heme thiolate proteins: e.g. heme sensing 7) Diversity of ET partners and complexes
F. Hannemann et al. BBA 1770 (2007) 330–344 Biological variations of electron transport chains
6) Heme thiolate proteins: e.g. heme sensing 7) Diversity of ET partners and complexes • 8) Regulation: interactions between different pathways • phenobarbital induction, sex-dependence • - drug – cholesterol biosynthesis • - drug – basic energy metabolism • - drug – lipid metablism • Need for application of systems biology - regulation by mikroRNAs and DNA methylation New regulatory level
9) P450s as tumor markers new drug targets Activation of prodrugs in the tumor cell
NOsynthase CYP11A1,B CYP17 CYP19 CYP21A2 CYP7B1 CYP26A1,B1,C1 CYP27A1, B1, C1 CYP24 Retinoic acid CYP51 CYP7A1 CYP27A1 CYP46 CYP39 Steroid(hormone)s Vitamin D CYP5A1 CYP8 A1,B1 Endogenous Substrates Arachidonic acid Sterols CYP CYP4 A(11,22),B1,F(2,3,8,12,22), V2,X1,Z1 Xenobiotics CYP1A1, A2, B1 CYP3A (4,5,7, 43) CYP2 A(6,7,13),B6,C(8,9,18,19)D6,E1,F1,J2,R1,S1,U1,W1 From: Inge Schuster
NOsynthase CYP11A1,B CYP17 CYP19 CYP21A2 CYP7B1 CYP26A1,B1,C1 CYP27A1, B1, C1 CYP24 Retinoic acid CYP51 CYP7A1 CYP27A1 CYP46 CYP39 Steroid(hormone)s Vitamin D CYP5A1 CYP8 A1,B1 Endogenous Substrates Arachidonic acid Sterols CYP CYP4 A(11,22),B1,F(2,3,8,12,22), V2,X1,Z1 Xenobiotics CYP1A1, A2, B1 CYP3A (4,5,7, 43) CYP2 A(6,7,13),B6,C(8,9,18,19)D6,E1,F1,J2,R1,S1,U1,W1 From: Inge Schuster
8) P450s as tumor markers new drug targets Activation of prodrugs in the tumor cell 9) Role in disease: Fungal resistance, breast cancer treatment (new targets by understanding regulation)
10) Engineering of P450s for biotechnological application • P450BM-3 approaches non-heme monooxygenases in • their propane and ethan hydroxylation ability • - Use of P450 for the phytoremediation of explosives • use of P450 for the production of the anti-malaria drug • artemisinin
Open questions – new challenges • Oxygen activation mechansim in various systems • 3D structure of mitochondrial P450s • Will solid-state NMR help us a lot? • Interaction, ET, gating? • 3D structures of ET complexes with P450 or of • P450 complexes with other interacting proteins • 5) Function of all 57 human P450s • 6) Role in neurobiology (CYP46, others?) • 7) Role in cardiovascular diseases • 8) Personalized drug therapy • 9) P450s as drug targets • 10)Sustainable biotechnological application of P450s
broad and sturdy side (wall) • tusk (spear) • trunk (snake) • knee (tree) • Ear (fan) • tail (rope)
Thank you, Damjana! Thanks to all members of the Organizing Committee!