Identification of dynamic oxygen access channels in 12/15-lipoxygenase [Elektronische Ressource] : molecular dynamics simulations and free energy landscapes / von Jan Saam

Identification of dynamic oxygen accesschannels in 12/15-lipoxygenaseMolecular dynamics simulations and free-energy landscapesDISSERTATIONzur Erlangung des akademischen Gradesdoctor rerum naturalium(Dr. rer. nat.)im Fach Biophysikeingereicht an derMathematisch-Naturwissenschaftlichen Fakultät IHumboldt-Universität zu BerlinvonHerr Dipl.-Biophys. Jan Saamgeboren am 30.12.1972 in MünchenPräsident der Humboldt-Universität zu Berlin:Prof. Dr. Christoph MarkschiesDekan der Mathematisch-Naturwissenschaftlichen Fakultät I:Prof. Dr. Christian LimbergGutachter:1. Prof. Dr. Hermann-Georg Holzhütter2. Prof. Dr. Hartmut Kühn3. Priv. Doz. Dr. Jörg GrunenbergiiThe cover imageMain oxygen access channel in rabbit 12/15-lipoxygenase. The distri-bution of oxygen in lipoxygenase is shown in terms of free energy isosurfaces(yellow). Red arrows indicate the energetically most favorable oxygen accessroute connecting a high affinity region at the protein surface with the catalyticcenter. Above, the energy profile along this path is projected. The grey linemarks the level of the drawn energy isosurface.iiiAbstractCells contain numerous enzymes utilizing molecular oxygen for their reactions.Often, their active sites are buried deeply inside the protein which raises thequestion whether there are specific access channels guiding oxygen to the siteof catalysis.