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

Abstract

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.

Keywords

• cathepsin B
• schistosoma
• crystal structure
• cysteine protease
• drug design
• parasite
• protease inhibitor
• hemoglobinolysis
• Schistosoma
• structure-activity relationships
• substrate/Inhibitor specificity