Highlights of the meeting

1. 15th International Symposium on Cytochrome P450 Highlights of the meeting

2. 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

3. 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

4. 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

5. 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. 6) Heme thiolate proteins: e.g. heme sensing 7) Diversity of ET partners and complexes

7. F. Hannemann et al. BBA 1770 (2007) 330–344 Biological variations of electron transport chains

8. 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. 9) P450s as tumor markers  new drug targets Activation of prodrugs in the tumor cell 

10. 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

11. 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

12. 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)

13. 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

14. The high(est)light of the Conference

16. 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

17. Highlights?

18. broad and sturdy side (wall) • tusk (spear) • trunk (snake) • knee (tree) • Ear (fan) • tail (rope)

19. Thank you, Damjana! Thanks to all members of the Organizing Committee!