Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strains of group A streptococci known to secrete the nephritis strain-associated protein (NSAP), a plasminogen activator, were studied for their ability to produce APSGN in rabbits. A tissue cage model was used to monitor the secretion of NSAP at the focus of infection and histopathological examination of kidney tissue was used to determine glomerular pathology. Animals infected with NSAP positive strains exhibited NSAP deposits in the glomerular tissue by day 7 in the absence of antibody to this molecule with progressive pathology indicative of APSGN three weeks later. Animals infected with the NSAP negative streptococcal strain exhibited no abnormal pathology. The ability of NSAP to bind to kidney tissue suggested that it has unique nephrotropic properties; and its ability to activate plasminogen to plasmin, possibly in situ, suggests that much of the pathological events associated with APSGN may be initiated by plasmin activity.
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PMID:A streptococcal plasminogen activator in the focus of infection and in the kidneys during the initial phase of experimental streptococcal glomerulonephritis. 306 3

Two conformationally constrained templates have been designed to provide selective inhibitors of the coagulation cascade serine protease, Factor Xa (FXa). The most active inhibitor, 2,7-bis[(Z)-p-amidinobenzylidene)]-3,3,6,6-tetramethylcycloheptanone, exhibits a K(i) of 42 nM against FXa, with strong selectivity against thrombin (1000-fold), trypsin (300-fold) and plasmin (900-fold). With only two freely rotatable bonds, molecular modeling suggests that one amidine group is positioned into the S1 pocket, forming hydrogen bonds with the side chain of Asp189, similar to other amidine-based inhibitors, with the second benzamidine positioned into the S4 pocket in a position to form strong cation-pi bonding with the S4 aryl cage. We suggest that this interaction plays an important role in the specificity of these inhibitors against other serine proteases.
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PMID:Design and synthesis of highly constrained factor Xa inhibitors: amidine-substituted bis(benzoyl)--diazepan-2-ones and bis(benzylidene)-bis(gem-dimethyl)cycloketones. 1287 32

The plasminogen activator (PA) system is an extracellular proteolytic enzyme system associated with various physiological and pathophysiological processes. A large body of evidence support that among the various components of the PA system, urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitor-1 and -2 (PAI-1 and PAI-2) play a major role in tumor progression and metastasis. The binding of uPA with uPAR is instrumental for the activation of plasminogen to plasmin, which in turn initiates a series of proteolytic cascade to degrade the components of the extracellular matrix, and thereby, cause tumor cell migration from the primary site of origin to a distant secondary organ. The components of the PA system show altered expression patterns in several common malignancies, which have identified them as ideal diagnostic, prognostic, and therapeutic targets to reduce cancer-associated morbidity and mortality. This review summarizes the various components of the PA system and focuses on the role of uPA-uPAR in different biological processes especially in the context of malignancy. We also discuss the current state of knowledge of uPA-uPAR-targeted diagnostic and therapeutic strategies for various malignancies.
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PMID:Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications. 2948 86