The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin
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Data
2002-05-10
Autores
Abad, M. C.
Arni, R. K.
Grella, D. K.
Castellino, F. J.
Tulinsky, A.
Geiger, J. H.
Título da Revista
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Título de Volume
Editor
Elsevier B.V.
Resumo
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 B.V. Ltd. All rights reserved.
Descrição
Palavras-chave
angiogenesis, plasminogen, coagulation, Crystal structure, kringle domains
Como citar
Journal of Molecular Biology. London: Academic Press Ltd Elsevier B.V. Ltd, v. 318, n. 4, p. 1009-1017, 2002.