Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors

Horn, Martin; Jílková, Adéla; Vondrášek, Jiří; Marešová, Lucie; Caffrey, C. R.; Mareš, Michael

doi:https://dx.doi.org/10.1021/cb100411v

Number of the records: 1

Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors

1.

SYSNO ASEP	0360455
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Mapping the Pro-Peptide of the Schistosoma mansoni Cathepsin B1 Drug Target: Modulation of Inhibition by Heparin and Design of Mimetic Inhibitors
Author(s)	Horn, Martin (UOCHB-X)_{RID, ORCID} Jílková, Adéla (UOCHB-X)_{RID, ORCID} Vondrášek, Jiří (UOCHB-X)_{RID, ORCID} Marešová, Lucie (UOCHB-X)_RID Caffrey, C. R. (US) Mareš, Michael (UOCHB-X)_{RID, ORCID}
Number of authors	6
Source Title	ACS Chemical Biology. - : American Chemical Society - ISSN 1554-8929 Roč. 6, č. 6 (2011), s. 609-617
Number of pages	9 s.
Language	eng - English
Country	US - United States
Keywords	Schistosoma mansoni ; cathepsin B ; propeptide
Subject RIV	CE - Biochemistry
R&D Projects	GA203/09/1585 GA ČR - Czech Science Foundation (CSF)
	KJB400550516 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
	IAA400550705 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
CEZ	AV0Z40550506 - UOCHB-X (2005-2011)
UT WOS	000291896400011
DOI	10.1021/cb100411v
Annotation	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.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418
Year of Publishing	2012

Number of the records: 1