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Contributions of Understanding the Adenylate Kinase and Myristoylation Reactions in the Malaria Parasite Plasmodium Falciparum

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Contributions of Understanding the Adenylate Kinase and Myristoylation Reactions in the Malaria Parasite Plasmodium Falciparum Contributions to understanding adenylate kinase and myristoylation reactions in the malaria parasite Plasmodium falciparum A thesis submitted to the faculty of Biology and Chemistry (FB 08) in fulfilment of the requirements of the Doctor of Science Degree of Justus Liebig University Giessen, Germany By Jipeng Ma From Shaanxi, China September 2012 Declaration Declaration I declare that this thesis is my original work and other sources of information have been properly quoted. This work has not been previously presented to obtain any other degree from any other university. Ich erkläre: Ich habe die vorgelegte Dissertation selbständig und ohne unerlaubte fremde Hilfe und nur mit den Hilfen angefertigt, die ich in der Dissertation angegeben habe. Alle Textstellen, die wörtlich oder sinngemäß aus veröffentlichten Schriften entnommen sind, und alle Angaben, die auf mündlichen Auskünften beruhen, sind als solche kenntlich gemacht. Bei den von mir durchgeführten und in der Dissertation erwähnten Untersuchungen habe ich die Grundsätze guter wissenschaftlicher Praxis, wie sie in der „Satzung der Justus-Liebig-Universität Gießen zur Sicherung guter wissenschaftlicher Praxis“ niedergelegt sind, eingehalten. Giessen, 4 th , September 2012 ………………………………. I Dedication Dedication To my family II Examination committee The thesis was presented for examination on the 10th September 2012 to the faculty of Biology and Chemistry of the Justus Liebig University Giessen, Germany. This thesis was supervised by Prof. Dr. Katja Becker and Prof. Dr. Peter Friedhoff. The thesis defense examination committee was composed of: Prof. Dr. Katja Becker Biochemistry and Molecular Biology Interdisciplinary Research Centre (IFZ) Justus-Liebig-University Giessen Heinrich-Buff-Ring 26-32, 35392 Giessen Germany Prof. Dr. Peter Friedhoff Institute of Biochemistry Justus Liebig University Giessen Heinrich-Buff-Ring 58, 35392 Giessen Germany Prof. Dr. Eveline Baumgart-Vogt Institute of Anatomy and Cell Biology Justus Liebig University Giessen Aulweg 123, 35385 Giessen Germany Prof. Dr. Adriaan Dorresteijn Institute of Zoology and Developmental Biology Justus Liebig University Giessen Stephanstr. 24, 35390 Giessen Germany III Acknowledgements Acknowledgements In this part, I would like to thank many people. It is clear that without all of you, this work would have become much more difficult. First of all, I would like to sincerely thank Prof. Katja Becker for giving me the opportunity to study in her laboratory and for supervising my PhD project. Her exceptional ideas, profound knowledge, and continuous guidance and encouragement supported me during the whole time of my PhD project. I also wish to thank Prof. Dr. Peter Friedhoff for being my second supervisor and giving me valuable discussions and advice. Many thanks go to all outstanding members of Prof. Becker's group. To Dr. Stefan Rahlfs, I would say I owe my deepest gratitude to you for your professional supervision and assistance. You not only taught me a lot in the scientific field but also supported me to live a happy life in Germany. I also would like to thank Elisabeth Fisher for her excellent cell culture work. I wish to thank Marina Fisher for teaching me a lot in enzyme kinetics. Special thanks go to Michaela Stumpf for her professional assistance during crystallization experiments. I would also like to say thank you to Timothy D. Bostick for the efficient correction of my thesis. And I also thank Dr. Esther Jortzik for her valuable work of my paper revision. Many thanks go to Sebastian Kehr for his help with my experiments and especially for picking me up from the airport on my first day. Besides, I would like to thanks all other group members, including Rimma Iozef, Beate Hecker, Ulrike Burkhard-Zahrt, Jochen Bathke, Jette Pretzel, Janina Preuss, Franziska Mohring, Anne Röseler, and Kathleen Zocher for all the help you provided. Special thanks go to my best friends and colleagues, Dennis Matovu Kasozi, Lihui Wang, and Tao Zhang for your great ideas and discussions. I would like to give many thanks to my friends in Giessen. They are Puyan Zhao, Dilin Liu, Liang Li, Qing Zhao, Qianhui Dai, Wenyu Chen and Jiuce Sun. I cannot imagine my life without all of you. I appreciate all the encouragements from you in every difficult time. I would like to thank the China Scholarship Council for giving me this opportunity to study in Germany and their generous financial support throughout my PhD study. Finally, I would like to thank all my family members for their support. I am greatly indebted to my mother, father, and younger brother. They inspire me to pursue my dream no matter when or where I am. I feel grateful to my family with their sacrifices and encouragements. IV List of Publications List of Publications 1. Ma J , Rahlfs S, Jortzik E, Heiner Schirmer R, Przyborski JM, Becker K. (2012). Subcellular localization of adenylate kinases in Plasmodium falciparum . FEBS Lett. Online 17 July 2012 [ahead of print.] 2. Jortzik E, Wang L, Ma J , Becker K (2012). Flavins and flavoproteins – applications in medicine. In: Meth Mol Biol, Humana Press USA, in press. Conferences and Scientific Meetings 1. Ma J , Rahlfs S, Przyborski JM, Schirmer RH, Becker K ( 2012 ). Characterization and localization of adenylate kinases in Plasmodium . Tropical Medicine and Parasitology, 25 th Annual Meeting German Society for Parasitology , Heidelberg, March 14 th -17 th , 2012. 2. Ma J , Rahlfs S, Przyborski JM, Schirmer RH, Becker K ( 2011 ). Characterization and localization of adenylate kinases in Plasmodium . 4th Annual Conference of the International Giessen Graduate School for the Life Sciences (GGL) , Giessen, September 21 st -22 nd , 2011. 3. Ma J , Rahlfs S, Przyborski JM, Schirmer RH, Becker K ( 2010 ). Characterization and localization of adenylate kinases in Plasmodium . 3th Annual Conference of the International Giessen Graduate School for the Life Sciences (GGL) , Giessen, September 29 th -30 th , 2010. 4. Ma J , Rahlfs S, Przyborski JM, Schirmer RH, Becker K ( 2010 ). A new adenylate kinase in Plasmodium - biochemical characterization and localization. Joint Meeting of the German Societies of Parasitology and Protozoology , Düsseldorf, March 17 th -20 th , 2010. 5. Ma J , Rahlfs S, Przyborski JM, Schirmer RH, Becker K ( 2009 ). A new adenylate kinase in Plasmodium -biochemical characterization and localization. "New Trends in Infectious Disease Research" 5 th Joint Ph.D Students Meeting of the Collaborative Research Centers SFB 544 Heidelberg, SFB 630 Würzburg and SFB 766 Tübingen , Heidelberg, November 19 th -21 st , 2009. V Table of Contents Table of Contents Declaration.................................................................................................................... I Dedication .................................................................................................................... II Acknowledgements ................................................................................................... IV List of Publications ..................................................................................................... V Conferences and Scientific Meetings ......................................................................... V Table of Contents ...................................................................................................... VI List of Figures ............................................................................................................ IX List of Tables .............................................................................................................. XI List of Abbreviations ................................................................................................ XII Summary ………………………………………………………………………….XIV Zusammenfassung.................................................................................................. XVI 1. Introduction .............................................................................................................. 1 1.1 Malaria ...................................................................................................................................... 1 1.1.1 Malaria: Past and present ......................................................................................... 1 1.1.2 Life cycle of Plasmodium falciparum ...................................................................... 2 1.1.3 Antimalarial drugs and malaria vaccine for malaria control .................................... 4 1.2 Adenylate kinase ....................................................................................................................... 7 1.2.1 Molecular and biochemical properties of adenylate kinase ..................................... 7 1.2.2 Structure and catalysis of adenylate kinase .............................................................. 8 1.2.3 Energy metabolism and signal pathway ................................................................. 11 1.2.4 Adenylate kinase in Plasmodium ........................................................................... 15 1.3 Myristoylation and N-myristoyltransferase ......................................................................... 17 1.3.1 Protein lipidation .................................................................................................... 17 1.3.2 Protein myristoylation event .................................................................................. 18 1.3.3 Click reaction in myristoylation research ..............................................................
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