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Blood coagulation is initiated by the interaction of factor VIIa (FVIIa) with membrane-bound tissue factor (TF) to form the extrinsic tenase complex which activates FX to FXa. Thus, it is an important target for the development of novel anticoagulants. Here, we report the isolation and characterization of a novel anticoagulant ringhalexin from the venom of <jats:italic>Hemachatus haemachatus<\/jats:italic> (African Ringhals Cobra). Amino acid sequence of the protein indicates that it belongs to the three-finger toxin family and exhibits 94% identity to an uncharacterized Neurotoxin-like protein NTL2 from <jats:italic>Naja atra<\/jats:italic>. Ringhalexin inhibited FX activation by extrinsic tenase complex with an IC<jats:sub>50<\/jats:sub> of 123.8\u2009\u00b1\u20099.54\u2009nM. It is a mixed-type inhibitor with the kinetic constants, Ki and Ki\u2019 of 84.25\u2009\u00b1\u20093.53\u2009nM and 152.5\u2009\u00b1\u200911.32\u2009nM, respectively. Ringhalexin also exhibits a weak, irreversible neurotoxicity on chick biventer cervicis muscle preparations. Subsequently, the three-dimensional structure of ringhalexin was determined at 2.95\u2009\u00c5 resolution. This study for the first time reports the structure of an anticoagulant three-finger toxin. Thus, ringhalexin is a potent inhibitor of the FX activation by extrinsic tenase complex and a weak, irreversible neurotoxin.<\/jats:p>","DOI":"10.1038\/srep25935","type":"journal-article","created":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T09:36:09Z","timestamp":1463132169000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex"],"prefix":"10.1038","volume":"6","author":[{"given":"Bhaskar","family":"Barnwal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chacko","family":"Jobichen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vallerinteavide Mavelli","family":"Girish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Shin","family":"Foo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Sivaraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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