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Visualizing Angiogenesis. A CREST Initiative. Elise A. Pellmann – Marquette University Daniel Sem, Ph.D. – Concordia University Wisconsin David Goodsell, Ph.D. – Scripps Research Institute. 1. Cellular landscape. 2. Movie. 1. Cellular landscape. 2 x 10 7 magnification Show:
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Visualizing Angiogenesis • A CREST Initiative Elise A. Pellmann – Marquette University Daniel Sem, Ph.D. – Concordia University Wisconsin David Goodsell, Ph.D. – Scripps Research Institute
1. Cellular landscape 2. Movie
1. Cellular landscape • 2 x 107 magnification • Show: • MAPK and receptor tyrosine kinase signaling • VEGF, plurality of biochemical cascades • angiogenesis • cell permeability
Knowledge needed for landscape • pathway: which proteins? • size, domain arrangement/shape, assembly, modifications, interactions/function
PyMOL, 3D Show: drug binding to DUSP-5 2. Movie
ERK-2 phosphatase: P-T183, P-Y185 C-terminal phosphatase domain N-terminal ERK-binding domain linker region Ser to Pro mutation (hemangiomas) DUSP-5
C: PDB 2G6Z • N: Homology model, NMR • Linker: hand-drawn • Domain orientation: good guess? N DUSP-5 model + + ERK-binding domain – – C catalytic domain
ERK binding • catalytic domain “clamps” down • phosphates removed from ERK N DUSP-5 model Drug impedes catalytic action, may also prevent ERK binding if DUSP-5 clamps down on drug + + ERK-binding domain – – C catalytic domain
Daniel Sem, Terrence Neumann, Prachi Pradeep David Goodsell Margaret Franzen, MSOE CREST grant Thank you Movie viewing