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Statements

Subject Item
n2:RIV%2F61388963%3A_____%2F11%3A00360455%21RIV12-AV0-61388963
rdf:type
n6:Vysledek skos:Concept
dcterms:description
Blood flukes of the genus Schistosoma cause the disease schistosomiasis that infects over 200 million people worldwide. Schistosoma mansoni cathepsin B1 (SmCB1) is a gut-associated protease that digests host blood proteins as source of nutrients. Enzymatic activity of the SmCB1 zymogen is prevented by the pro-peptide that sterically blocks the active site until activation of the zymogen to the mature enzyme. We investigated the structure-inhibition relationships of how the SmCB1 pro-peptide interacts with the enzyme core using a SmCB1 zymogen model and pro-peptide-derived synthetic fragments. Two regions were identified within the pro-peptide that govern its inhibitory interaction with the enzyme core: an 'active site region' and a unique 'heparin-binding region' that requires heparin. Using the active site region as a template and a docking model of SmCB1, we designed a series of inhibitors mimicking the pro-peptide structure. Blood flukes of the genus Schistosoma cause the disease schistosomiasis that infects over 200 million people worldwide. Schistosoma mansoni cathepsin B1 (SmCB1) is a gut-associated protease that digests host blood proteins as source of nutrients. Enzymatic activity of the SmCB1 zymogen is prevented by the pro-peptide that sterically blocks the active site until activation of the zymogen to the mature enzyme. We investigated the structure-inhibition relationships of how the SmCB1 pro-peptide interacts with the enzyme core using a SmCB1 zymogen model and pro-peptide-derived synthetic fragments. Two regions were identified within the pro-peptide that govern its inhibitory interaction with the enzyme core: an 'active site region' and a unique 'heparin-binding region' that requires heparin. Using the active site region as a template and a docking model of SmCB1, we designed a series of inhibitors mimicking the pro-peptide structure.
dcterms:title
Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors
skos:prefLabel
Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors
skos:notation
RIV/61388963:_____/11:00360455!RIV12-AV0-61388963
n6:predkladatel
n15:ico%3A61388963
n3:aktivita
n13:Z n13:I n13:P
n3:aktivity
I, P(GA203/09/1585), P(IAA400550705), P(KJB400550516), Z(AV0Z40550506)
n3:cisloPeriodika
6
n3:dodaniDat
n10:2012
n3:domaciTvurceVysledku
n5:9846476 n5:7667108 n5:1888986 n5:7358946 n5:8133859
n3:druhVysledku
n19:J
n3:duvernostUdaju
n11:S
n3:entitaPredkladatele
n7:predkladatel
n3:idSjednocenehoVysledku
210640
n3:idVysledku
RIV/61388963:_____/11:00360455
n3:jazykVysledku
n18:eng
n3:klicovaSlova
Schistosoma mansoni; cathepsin B; propeptide
n3:klicoveSlovo
n4:Schistosoma%20mansoni n4:propeptide n4:cathepsin%20B
n3:kodStatuVydavatele
US - Spojené státy americké
n3:kontrolniKodProRIV
[FE09680467A8]
n3:nazevZdroje
ACS Chemical Biology
n3:obor
n20:CE
n3:pocetDomacichTvurcuVysledku
5
n3:pocetTvurcuVysledku
6
n3:projekt
n8:GA203%2F09%2F1585 n8:KJB400550516 n8:IAA400550705
n3:rokUplatneniVysledku
n10:2011
n3:svazekPeriodika
6
n3:tvurceVysledku
Horn, Martin Caffrey, C. R. Jílková, Adéla Mareš, Michael Marešová, Lucie Vondrášek, Jiří
n3:wos
000291896400011
n3:zamer
n16:AV0Z40550506
s:issn
1554-8929
s:numberOfPages
9
n12:doi
10.1021/cb100411v