title: Amino acid sequence and homology modeling of obtustatin, a novel non-RGD-containing short disintegrin isolated from the venom of Vipera lebetina obtusa.
abstract: Disintegrins represent a group of cysteine-rich peptides occurring in Crotalidae and Viperidae snake venoms, and are potent antagonists of several integrin receptors. A novel disintegrin, obtustatin, was isolated from the venom of the Vipera lebetina obtusa viper, and represents the first potent and selective inhibitor of the binding of integrin alpha(1)beta(1) to collagen IV. The primary structure of obtustatin contains 41 amino acids and is the shortest disintegrin described to date. Obtustatin shares the pattern of cysteines of other short disintegrins. However, in contrast to known short disintegrins, the integrin-binding loop of obtustatin is two residues shorter and does not express the classical RGD sequence. Using synthetic peptides, a KTS motif was identified as the integrin-binding sequence. A three-dimensional model of obtustatin, built by homology-modeling structure calculations using different templates and alignments, strongly indicates that the novel KTS motif may reside at the tip of a flexible loop.
authors.affiliation: Instituto de Biomedicina de Valencia, C.S.I.C., Spain.
authors.forename: M Paz
authors.initials: MP
authors.lastname: Moreno-Murciano
authors.forename: Daniel
authors.initials: D
authors.lastname: Monleón
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calvete
authors.forename: Bernardo
authors.initials: B
authors.lastname: Celda
authors.forename: Cezary
authors.initials: C
authors.lastname: Marcinkiewicz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019483:Disintegrins / Q000737:chemistry* / Q000302:isolation & purification*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides; D014757:Viper Venoms / Q000737:chemistry* / Q000302:isolation & purification*; D017819:Viperidae
chemical_list: D019483:Disintegrins; D009842:Oligopeptides; D014757:Viper Venoms; C474313:obtustatin, Vipera lebetina obtusa; C047981:arginyl-glycyl-aspartic acid