Structural Basis for Inhibition of Cathepsin B Drug Target from the Human Blood Fluke, Schistosoma mansoni

0365166 - ÚOCHB 2012 RIV US eng J - Journal Article
Jílková, Adéla - Řezáčová, Pavlína - Lepšík, Martin - Horn, Martin - Váchová, Jana - Fanfrlík, Jindřich - Brynda, Jiří - McKerrow, J. H. - Caffrey, C. R. - Mareš, Michael
Structural Basis for Inhibition of Cathepsin B Drug Target from the Human Blood Fluke, Schistosoma mansoni.
Journal of Biological Chemistry. Roč. 286, č. 41 (2011), s. 35770-35881. ISSN 0021-9258. E-ISSN 1083-351X
R&D Projects: GA ČR GA203/09/1585; GA ČR GAP208/11/0295; GA MŠMT OC09007
Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514
Keywords : cathepsin B * schistosoma * crystal structure
Subject RIV: CC - Organic Chemistry
Impact factor: 4.773, year: 2011

We determined three crystal structures of Schistosoma mansoni cathepsin B1 (SmCB1) in complex with peptidomimetic inhibitors. A panel of vinyl sulfone inhibitors was screened in vitro with SmCB1 and in a schistosomula assay; severity of phenotype induced in the parasite correlated with enzyme inhibition. Substrate specificity of SmCB1 was analyzed using synthetic peptides and the natural substrate, hemoglobin.
Permanent Link: http://hdl.handle.net/11104/0200472