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

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Presentation transcript:

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. Movie 1. Cellular landscape

2 x 10 7 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

Pathway: KEGG

Pathway

Proteins (i)

Proteins (ii)

Sketches

Final version

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

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

DUSP-5 model C N catalytic domain ERK-binding domain + + – – 1.ERK binding 2.catalytic domain “clamps” down 3.phosphates removed from ERK Drug impedes catalytic action, may also prevent ERK binding if DUSP-5 clamps down on drug

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