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http://purl.uniprot.org/citations/7744780http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7744780http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/7744780http://www.w3.org/2000/01/rdf-schema#comment"Angiotensinogen exhibits genetic linkage to and association with essential hypertension and preeclampsia, a common hypertensive disorder of pregnancy; however, the polymorphisms detected thus far provide no functional clues. In a preeclamptic patient, we have identified a mutation leading to the replacement of leucine by phenylalanine at position 10 of mature angiotensinogen (L10F), the site of renin cleavage. Kinetic analyses of the enzymes of the renin-angiotensin system, using either model peptides or full-length substrates, show that this mutation significantly alters the reactions with both renin and angiotensin-converting enzyme. For the renin reaction on a full-length substrate, this substitution leads to a 10-fold decrease in Km (from 1.1 to 0.09 microM) and a 5-fold decrease in kcat (from 1.0 to 0.22 s-1); as a result, catalytic efficiency (kcat/Km) is increased by a factor of 2 (1.1 versus 2.4 microM-1 s-1). In the reaction of angiotensin-converting enzyme on angiotensin decapeptides, the substitution has no effect on Km (38.0 versus 30.0 microM), but increases kcat and catalytic efficiency > 2-fold (kcat = 15.0 versus 37.0 s-1; kcat/Km = 0.41 versus 1.23). The renin-angiotensin system, challenged by the profound physiological adaptations of pregnancy, is perturbed in preeclampsia; consequently, the L10F mutation may promote this condition in carrier subjects."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.org/dc/terms/identifier"doi:10.1074/jbc.270.19.11430"xsd:string
http://purl.uniprot.org/citations/7744780http://purl.org/dc/terms/identifier"doi:10.1074/jbc.270.19.11430"xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Inoue I."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Inoue I."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Lifton R.P."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Lifton R.P."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Corvol P."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Corvol P."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Jeunemaitre X."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Jeunemaitre X."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Bohlender J."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Bohlender J."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Crain P."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Crain P."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Helin C."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Helin C."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Lalouel J.-M."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Lalouel J.-M."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Rohrwasser A."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Rohrwasser A."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Ward K."xsd:string
http://purl.uniprot.org/citations/7744780http://purl.uniprot.org/core/author"Ward K."xsd:string