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Publication Abstract from PubMed

Extant disintegrins represent a family of polypeptides found in the venoms of Viperidae and Crotalidae snakes (vipers and rattlesnakes) that block potently and with high degree of selectivity the function of beta1 and beta3 integrin receptors. This toxin family owes its origin to the neofunctionalization of the extracellular region of an ADAM 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-sized, dimeric, and short disintegrins, involved the stepwise loss of pairs of class-specific disulfide linkages and the processing of the N-terminal region. NMR and crystal structures of medium-sized, dimeric, and short disintegrins have been solved. However, the structure of a long disintegrin was missing. The here reported NMR solution structures of two disulfide bond conformers of the long disintegrin bitistatin, from the African puff adder Bitis arietans, provide insights into how a structural domain of the extracellular region of an ADAM molecule recruited, and selectively expressed into the snake venom gland proteome as a PIII metalloprotease in the Jurassic has been since tranformed into a family of integrin receptor antagonists. This article is protected by copyright. All rights reserved.

NMR structure of bitistatin, a missing piece in the evolutionary pathway of snake venom disintegrins.,Carbajo RJ, Sanz L, Perez A, Calvete JJ FEBS J. 2014 Nov 1. doi: 10.1111/febs.13138. PMID:25363287^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.