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• W2160099802 endingPage "236" @default.
• W2160099802 startingPage "221" @default.
• W2160099802 abstract "Tissue-type plasminogen activator (t-PA), a 65 kDa member of the chymotrypsin family of serine proteases, catalyzes the rate-limiting step in the endogenous fibrinolytic cascade: conversion of the zymogen plasminogen into the active enzyme plasmin.‘-” Plasmin, a serine protease of relatively broad specificity, efficiently degrades the fibrin that forms the meshwork of a thrombus or blood clot.‘-3 The fibrinolytic cascade, therefore, provides an important counterbalance in vivo to the blood coagulation cascade. Appreciation that inappropriate thrombosis was the focal event in the initiation of acute myocardial infarction, and the demonstration that timely administration of thrombolytic agents could restore patency to occluded coronary arteries sparked great interest in thrombolytic therapy, the endogenous fibrinolytic system and, in particular, the plasminogen activators. Current thrombolytic therapy achieves lysis of stable coronary thrombi through the intravenous administration of plasminogen activators, usually either human t-PA or the bacterial protein, streptokinase.‘.” The evidence that thrombolytic therapy is capable of rapidly lysing thrombi without undue risk of hemorrhage is now convincing; numerous studies and clinical trials have confirmed both the efficacy and the safety of thrombolytic agents in the treatment of patients with an evolving myocardial infarction.4-‘2 t-PA is synthesized and secreted by vascular endothelial cells.’ 3-16 The amino acid sequence of the human t-PA precursor, originally deduced from the nucleotide sequence of cloned cDNAs”,‘~ and subsequently confirmed by amino acid sequencing of the purified proteinI consists of 563 amino acids. As this precursor is transported along the secretory pathway, oligosaccharide groups are added at three positions (Asn 117, Asn 184, and Asn 448), and both a hydrophobic signal sequence and a hydrophilic prosequence are removed by endopeptidic cleavage. ‘9-2’ The resulting 527 amino" @default.
• W2160099802 created "2016-06-24" @default.
• W2160099802 creator A5062861984 @default.
• W2160099802 date "1994-01-01" @default.
• W2160099802 modified "2023-09-27" @default.
• W2160099802 title "Probing structure-function relationships of tissue-type plasminogen activator by site-specific mutagenesis" @default.
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