The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin.
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Abad MC, Arni RK, Grella DK, Castellino FJ, Tulinsky A, Geiger JH
The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin.
J Mol Biol. 2002 May 10;318(4):1009-17.
- PubMed ID
- 12054798 [ View in PubMed]
- Abstract
Angiogenesis inhibitors have gained much public attention recently as anti-cancer agents and several are currently in clinical trials, including angiostatin (Phase I, Thomas Jefferson University Hospital, Philadelphia, PA). We report here the bowl-shaped structure of angiostatin kringles 1-3, the first multi-kringle structure to be determined. All three kringle lysine-binding sites contain a bound bicine molecule of crystallization while the former of kringle 2 and kringle 3 are cofacial. Moreover, the separation of the kringle 2 and kringle 3 lysiner binding sites is sufficient to accommodate the alpha-helix of the 30 residue peptide VEK-30 found in the kringle 2/VEK-30 complex. Together the three kringles produce a central cavity suggestive of a unique domain where they may function in concert.