Crystal structure and chemical inhibition of essential schistosome host-interactive virulence factor carbonic anhydrase SmCA.

ABSTRACT: The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Here we identify an α-carbonic anhydrase (SmCA) that is expressed at the schistosome surface as determined by activity assays and immunofluorescence/immunogold localization. Suppressing SmCA expression by RNAi significantly impairs the ability of larval parasites to infect mice, validating SmCA as a rational drug target. Purified, recombinant SmCA possesses extremely rapid CO₂ hydration kinetics (k_cat: 1.2 × 10⁶ s^-1; k_cat/K_m: 1.3 × 10⁸ M^-1s^-1). The enzyme's crystal structure was determined at 1.75 Å resolution and a collection of sulfonamid

SUBMITTER: Da'dara AA 

PROVIDER: S-EPMC6728359 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature