{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:56:50Z","timestamp":1760144210090,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T00:00:00Z","timestamp":1711756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Abnormal blood coagulation is a major health problem and natural anticoagulants from blood-feeding organisms have been investigated as novel therapeutics. NAPc2, a potent nematode-derived inhibitor of coagulation, has an unusual mode of action that requires coagulation factor Xa but does not inhibit it. Molecular dynamics simulations of NAPc2 and factor Xa were generated to better understand NAPc2. The simulations suggest that parts of NAPc2 become more rigid upon binding factor Xa and reveal that two highly conserved residues form an internal salt bridge that stabilises the bound conformation. Clotting time assays with mutants confirmed the utility of the salt bridge and suggested that it is a conserved mechanism for stabilising the bound conformation of secondary structure-poor protease inhibitors.<\/jats:p>","DOI":"10.3390\/biom14040421","type":"journal-article","created":{"date-parts":[[2024,3,31]],"date-time":"2024-03-31T13:42:30Z","timestamp":1711892550000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in Internal Structure and Dynamics upon Binding Stabilise the Nematode Anticoagulant NAPc2"],"prefix":"10.3390","volume":"14","author":[{"given":"Elaine","family":"Woodward","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7034-8374","authenticated-orcid":false,"given":"Brendan M.","family":"Duggan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e480","DOI":"10.1161\/CIRCULATIONAHA.108.841403","article-title":"The Surgeon General\u2019s Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism","volume":"119","author":"Rathbun","year":"2009","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1161\/CIRCULATIONAHA.106.685974","article-title":"Beyond Unfractionated Heparin and Warfarin: Current and Future Advances","volume":"116","author":"Hirsh","year":"2007","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1073\/pnas.93.5.2149","article-title":"Anticoagulant repertoire of the hookworm Ancylostoma caninum","volume":"93","author":"Stassens","year":"1996","journal-title":"Proc. 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