Stephen G . McCance

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Recently we have identified angiostatin, an endogenous angiogenesis inhibitor of 38 kDa which specifically blocks the growth of endothelial cells (O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C. , Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, E. H., and Folkman, J. (1994) Cell 79, 315-328; Folkman, J. (1995) Nat. Med. 1, 27-31). Angiostatin(More)
Yihai Cao, Richard W. Ji, Don Davidson, Johann Schaller, Daniel Marti, Sabine Söhndel, Stephen G. McCance, Michael S. O’Reilly, Miguel Llinás, and Judah Folkman From the Departments of Surgery and Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, the Pharmaceutical Products Division, Aging and Degenerative Diseases Research, Abbott(More)
In order to identify the individual contributions of the kringle (K) domains of human plasminogen (Pg) to the epsilon-aminocaproic acid (EACA) induced stimulation of Pg activation by low-molecular-weight urokinase-type plasminogen activator (LMW-uPA) and inhibition of this same activation by Cl-, we constructed the most conservative recombinant- (r-) Pg(More)
The X-ray crystal structure of the recombinant (r) kringle 5 domain of human plasminogen (K5HPg) has been solved by molecular replacement methods using K1HPg as a model and refined at 1.7 A resolution to an R factor of 16.6%. The asymmetric unit of K5HPg is composed of two molecules related by a noncrystallographic 2-fold rotation axis approximately(More)
The mature form of the zymogen, human plasminogen (HPlg), contains 791 amino acids present in a single polypeptide chain. The fibrinolytic enzyme, human plasmin (HPlm), is formed from HPlg as a result of activator-catalysed cleavage of the Arg561-Val562 peptide bond in HPlg. The resulting HPlm contains a heavy chain of 561 amino acid residues, originating(More)
As part of continuing studies to evaluate whether the kringle domain regions of human plasminogen (HPg) exhibit independent conformational properties, simple model systems are required. Toward this end, we have constructed cDNA regions of HPg encoding its kringle 4 ([K4HPg]) and kringle 4-5 ([K4HPgK5HPg]) regions, expressed these gene fragments in bacterial(More)
Regions of the human plasminogen (Pg) cDNA containing its kringle 4 (K4) and K5 domains have been expressed in Escherichia coli, and binding constants of omega-amino acid ligands for recombinant (r)-[K4Pg] and r-[K5Pg] have been obtained. In each case, the results showed that of a series of aliphatic alpha, omega-amino acid analogues, 6-aminohexanoic acid(More)
The roles of each of the three omega-amino acid-binding kringles (K) of Glu1-Pg, viz., [K1Pg], [K4Pg], and [K5Pg], in engendering the Cl(-)-induced alteration to its tight (T) conformation and in effecting the epsilon-aminocaproic acid (EACA)-mediated change to the relaxed (R) protein conformation have been investigated by mutagenesis strategies wherein the(More)
Regions of the human plasminogen (Pg) cDNA containing its kringle 4 (K4) and K5 domains have been expressed in Escherichia coli, and binding constants of oamino acid ligands for recombinant (r)-[K4,,] and r-[K5,,] have been obtained. In each case, the results showed that of a series of aliphatic a,o-amino acid analogues, 6-aminohexanoic acid showed maximal(More)
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