Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 318, Issue 4, Pages 1009-1017Publisher
ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
DOI: 10.1016/S0022-2836(02)00211-5
Keywords
angiogenesis; plasminogen; coagulation; crystal structure; kringle domains
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Funding
- NHLBI NIH HHS [HL13423, HL25942, HL43229] Funding Source: Medline
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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 a-helix of the 30 residue pepticle 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. (C) 2002 Elsevier Science Ltd. All rights reserved.
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