{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T17:58:09Z","timestamp":1781027889966,"version":"3.54.1"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health, National Institute of Allergy and Infectious Diseases","award":["AI137667"],"award-info":[{"award-number":["AI137667"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Schistosomiasis, a parasitic disease caused by worms of the genus Schistosoma, affects &gt;250 million people worldwide. With no available vaccine, treatment relies solely on one drug\u2014praziquantel\u2014underscoring the urgent need for new therapies. We identified a tegumental, non-neuronal acetylcholinesterase (AChE) from Schistosoma mansoni\u2014SmTAChE\u2014as a promising drug target. RNA interference confirmed its essential role in parasite survival, as gene suppression significantly reduced parasite recovery from infected animals. Here, we produced functionally active recombinant SmTAChE by using a mammalian expression system. Biochemical characterization confirmed its identity as a true acetylcholinesterase, with the highest turnover rate (Kcat = 373 \u00b1 39 s\u22121) and catalytic efficiency (Kcat\/Km = 1.17 \u00d7 106 M\u22121\u00b7S\u22121) for acetylthiocholine. Additionally, rSmTAChE was inhibited by classical AChE-specific inhibitors but not by a butyrylcholinesterase-specific inhibitor. To identify novel SmTAChE inhibitors, we developed a high-throughput chemical screening protocol (Z\u2032 factor &gt; 0.9) and screened a 1894-compound validation library. Twelve compounds reproducibly inhibited rSmTAChE by &gt;30% at 7.5 \u00b5M, including known AChE inhibitors like physostigmine and new selective inhibitors. Notably, compound #2 preferentially inhibited rSmTAChE (IC50 = 0.74 \u00b5M) over human AChE (IC50 = 151 \u00b5M), thus providing a foundation for developing parasite-specific therapies targeting SmTAChE and potentially leading to new treatments for schistosomiasis.<\/jats:p>","DOI":"10.3390\/ijms26051975","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T06:13:18Z","timestamp":1740463998000},"page":"1975","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expression, Characterization and Selective Chemical Inhibition of Essential Schistosoma mansoni Tegumental Acetylcholinesterase (SmTAChE)"],"prefix":"10.3390","volume":"26","author":[{"given":"Patrick J.","family":"Skelly","sequence":"first","affiliation":[{"name":"Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-9623","authenticated-orcid":false,"given":"Akram A.","family":"Da\u2019dara","sequence":"additional","affiliation":[{"name":"Molecular Helminthology Laboratory, Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S1473-3099(06)70521-7","article-title":"Schistosomiasis and water resources development: Systematic review, meta-analysis, and estimates of people at risk","volume":"6","author":"Steinmann","year":"2006","journal-title":"Lancet Infect. 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