Probing dimerization and structural flexibility Probing dimerization - PowerPoint PPT Presentation

European Molecular Biology Laboratory Hamburg Outstation European Molecular Biology Laboratory Hamburg Outstation European Molecular Biology Laboratory Hamburg Outstation European Molecular Biology Laboratory Hamburg Outstation BioSAXS group BioSAXS group BioSAXS group BioSAXS group Probing dimerization and structural flexibility Probing dimerization and structural flexibility Probing dimerization and structural flexibility Probing dimerization and structural flexibility on mammalian lipoxygenases by SAXS on mammalian lipoxygenases by SAXS on mammalian lipoxygenases by SAXS on mammalian lipoxygenases by SAXS Dr. Weifeng Shang Dr. Weifeng Shang Dr. Weifeng Shang 尚伟峰 Dr. Weifeng Shang , , ., ., ., ., . . . . . (2011), . (2011), Shang Shang , Shang , W W W W ., ., et et et et al al al al ., ., J J . J J . Mol Mol Mol . Mol . Biol Biol Biol Biol . (2011), . (2011), Shang , in in press press press , , available , available available online online in in press available online online doi doi :10.1016/ :10.1016/ :10.1016/ :10.1016/ j j j . . . jmb . jmb jmb .2011.04.035 .2011.04.035 .2011.04.035 .2011.04.035 doi doi j jmb

outline outline outline outline 1 1 1 1 Introduction to Introduction to Introduction to Introduction to lipoxygenase lipoxygenase lipoxygenase lipoxygenase 2 SAXS 2 SAXS experiments and results experiments and results 2 SAXS 2 SAXS experiments and results experiments and results 3 3 Complementary techniques Complementary techniques 3 3 Complementary techniques Complementary techniques

mammalian lipoxygenases (LOX) mammalian lipoxygenases (LOX) mammalian lipoxygenases (LOX) mammalian lipoxygenases (LOX) Human LOX Human LOX Human LOX Human LOX hemeostasis drug target (structure-function relationship) Crystal structure in PDB Crystal structure in PDB Crystal structure in PDB Crystal structure in PDB plant LOXs fragment of human platelet type 12S-LOX rabbit 12/15LOX (accession code:2p0m)

human and rabbit LOX human and rabbit LOX human and rabbit LOX human and rabbit LOX Oligomeric form Oligomeric form Oligomeric form Oligomeric form r-15LOX (dimer in crystal, monomer in soution) hp-12LOX ( dimer in solution )

Wild type r-15LOX Wild type r-15LOX Wild type r-15LOX Wild type r-15LOX Wild type Wild type Wild type Wild type

Y98R mutant and double mutant Y98R mutant and double mutant Y98R mutant and double mutant Y98R mutant and double mutant

Oligomerization behaviors Oligomerization behaviors Oligomerization behaviors Oligomerization behaviors

Effect of ligand Effect of ligand Effect of ligand Effect of ligand

Data reduction Data reduction Data reduction Data reduction

Acknowledgement Acknowledgement Acknowledgement Acknowledgement