Structural highlights
Publication Abstract from PubMed
The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Here we identify an alpha-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 (kcat: 1.2 x 10(6) s(-1); kcat/Km: 1.3 x 10(8) M(-1)s(-1)). The enzyme's crystal structure was determined at 1.75 A resolution and a collection of sulfonamides and anions were tested for their ability to impede rSmCA action. Several compounds (phenylarsonic acid, phenylbaronic acid, sulfamide) exhibited favorable Kis for SmCA versus two human isoforms. Such selective rSmCA inhibitors could form the basis of urgently needed new drugs that block essential schistosome metabolism, blunt parasite virulence and debilitate these important global pathogens.
Crystal structure and chemical inhibition of essential schistosome host-interactive virulence factor carbonic anhydrase SmCA.,Da'dara AA, Angeli A, Ferraroni M, Supuran CT, Skelly PJ Commun Biol. 2019 Sep 5;2:333. doi: 10.1038/s42003-019-0578-0. eCollection 2019. PMID:31508507[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Da'dara AA, Angeli A, Ferraroni M, Supuran CT, Skelly PJ. Crystal structure and chemical inhibition of essential schistosome host-interactive virulence factor carbonic anhydrase SmCA. Commun Biol. 2019 Sep 5;2:333. doi: 10.1038/s42003-019-0578-0. eCollection 2019. PMID:31508507 doi:http://dx.doi.org/10.1038/s42003-019-0578-0
