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This is the first exogenous protein to antagonize \u03b2\u2010adrenergic receptors and thereby causing reduction in heart rates (bradycardia) when administered into animals, unlike the conventional cardiotoxins as reported earlier. 3FTXs are stable all \u03b2\u2010sheet peptides with 60\u201380 amino acid residues. Here, we describe the three\u2010dimensional crystal structure of \u03b2\u2010cardiotoxin together with the identification of a molten globule intermediate in the unfolding pathway of this protein. In spite of the overall structural similarity of this protein with conventional cardiotoxins, there are notable differences observed at the loop region and in the charge distribution on the surface, which are known to be critical for cytolytic activity of cardiotoxins. The molten globule intermediate state present in the thermal unfolding pathway of \u03b2\u2010cardiotoxin was however not observed during the chemical denaturation of the protein. Interestingly, circular dichroism (CD) and NMR studies revealed the presence of \u03b1\u2010helical secondary structure in the molten globule intermediate. These results point to substantial conformational plasticity of \u03b2\u2010cardiotoxin, which might aid the protein in responding to the sometimes conflicting demands of structure, stability, and function during its biological lifetime.<\/jats:p>","DOI":"10.1002\/pro.3605","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T07:34:42Z","timestamp":1553067282000},"page":"952-963","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of a \u03b1\u2010helical molten globule intermediate and structural characterization of \u03b2\u2010cardiotoxin, an all \u03b2\u2010sheet protein isolated from the venom of <i>Ophiophagus hannah<\/i> (king cobra)"],"prefix":"10.1002","volume":"28","author":[{"given":"Amrita","family":"Roy","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science National University of Singapore  Singapore 117543"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun","family":"Qingxiang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science National University of Singapore  Singapore 117543"},{"name":"Department of Pathology West China Hospital, Sichuan University  Chengdu China 610041"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chapeaurouge","family":"Alex","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science National University of Singapore  Singapore 117543"},{"name":"Funda\u00e7\u00e3o Oswaldo Cruz\u2010Cear\u00e1 Rua S\u00e3o Jos\u00e9, 2\u00b0 Pavimento, Precabura  Eus\u00e9bio 61760\u2010000 Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandhakishore","family":"Rajagopalan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science National University of Singapore  Singapore 117543"},{"name":"National Research Council of Canada  Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chacko","family":"Jobichen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science National University of Singapore  Singapore 117543"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Sivaraman","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science National University of Singapore  Singapore 117543"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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