title: The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin.
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.
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing 48824, USA.
authors.forename: Marta C
authors.initials: MC
authors.lastname: Abad
authors.forename: R K
authors.initials: RK
authors.lastname: Arni
authors.forename: Davida K
authors.initials: DK
authors.lastname: Grella
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
authors.forename: Alexander
authors.initials: A
authors.lastname: Tulinsky
authors.forename: James H
authors.initials: JH
authors.lastname: Geiger
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000737:chemistry*; D043168:Angiostatins; D003460:Crystallization; D018360:Crystallography, X-Ray; D006801:Humans; D018082:Kringles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry*; D010843:Pichia; D010958:Plasminogen / Q000737:chemistry*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen