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Visualizing Angiogenesis

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

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  1. Visualizing Angiogenesis • A CREST Initiative Elise A. Pellmann – Marquette University Daniel Sem, Ph.D. – Concordia University Wisconsin David Goodsell, Ph.D. – Scripps Research Institute

  2. 1. Cellular landscape 2. Movie

  3. 1. Cellular landscape • 2 x 107 magnification • Show: • MAPK and receptor tyrosine kinase signaling • VEGF, plurality of biochemical cascades • angiogenesis • cell permeability

  4. Knowledge needed for landscape • pathway: which proteins? • size, domain arrangement/shape, assembly, modifications, interactions/function

  5. Pathway: KEGG

  6. Pathway

  7. Proteins (i)

  8. Proteins (ii)

  9. Sketches

  10. Final version

  11. PyMOL, 3D Show: drug binding to DUSP-5 2. Movie

  12. 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

  13. C: PDB 2G6Z • N: Homology model, NMR • Linker: hand-drawn • Domain orientation: good guess? N DUSP-5 model + + ERK-binding domain – – C catalytic domain

  14. 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

  15. Daniel Sem, Terrence Neumann, Prachi Pradeep David Goodsell Margaret Franzen, MSOE CREST grant Thank you Movie viewing

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