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This toxin family owes its origin to the neofunctionalization of the extracellular region of an<jats:styled-content style=\"fixed-case\">ADAM<\/jats:styled-content>(a disintegrin and metalloprotease) molecule recruited into the snake venom gland proteome in the Jurassic. The evolutionary structural diversification of the disintegrin scaffold, from the ancestral long disintegrins to the more recently evolved medium\u2010sized, dimeric and short disintegrins, involved the stepwise loss of pairs of class\u2010specific disulfide linkages and the processing of the N\u2010terminal region.<jats:styled-content style=\"fixed-case\">NMR<\/jats:styled-content>and crystal structures of medium\u2010sized, dimeric and short disintegrins have been solved. However, the structure of a long disintegrin remained unknown. The present study reports the<jats:styled-content style=\"fixed-case\">NMR<\/jats:styled-content>solution structures of two disulfide bond conformers of the long disintegrin bitistatin from the African puff adder<jats:italic>Bitis\u00a0arietans<\/jats:italic>. The findings provide insight into how a structural domain of the extracellular region of an<jats:styled-content style=\"fixed-case\">ADAM<\/jats:styled-content>molecule, recruited into and selectively expressed in the snake venom gland proteome as a<jats:styled-content style=\"fixed-case\">PIII<\/jats:styled-content>metalloprotease in the Jurassic, has subsequently been tranformed into a family of integrin receptor antagonists.<\/jats:p>","DOI":"10.1111\/febs.13138","type":"journal-article","created":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T13:33:11Z","timestamp":1414848791000},"page":"341-360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["<scp>NMR<\/scp>structure of bitistatin\u00a0\u2013\u00a0a missing piece in the evolutionary pathway of snake venom disintegrins"],"prefix":"10.1111","volume":"282","author":[{"given":"Rodrigo 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