title: Amino acid structure and characterization of a heterodimeric disintegrin from Vipera lebetina venom.
abstract: A heterodimeric disintegrin designed as lebein was isolated from crude Vipera lebetina venom using gel filtration, anion and cation exchange chromatographies on FPLC. The amino acid sequence of each subunit determined by Edman degradation contains 64 residues with ten half-cystines and an RGD site at the C-terminal part of the molecule. The molecular mass of native lebein determined by mass spectrometry was found to be 14083.4 Da and those of alpha and beta subunits were 6992.05 and 7117.62, respectively. These value are in good agreement with those calculated from the sequences. This protein strongly inhibits ADP induced platelet aggregation on human platelet rich plasma with IC(50)=160 nM. Sequences of this protein subunits displayed significant sequence similarities with many other monomeric and dimeric disintegrins reported from snake venoms. We identified an amino acid residue (N) in the hairpin loop of both subunits (CNRARGDDMNDYC) which is different from all other reported motifs of disintegrins and this subtle difference may contribute to the distinct affinities and selectivities of this class of proteins.
authors.affiliation: Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Tunisia. ammar.gasmi@pasteur.rns.tn
authors.forename: A
authors.initials: A
authors.lastname: Gasmi
authors.forename: N
authors.initials: N
authors.lastname: Srairi
authors.forename: S
authors.initials: S
authors.lastname: Guermazi
authors.forename: H
authors.initials: H
authors.lastname: Dekhil
authors.forename: H
authors.initials: H
authors.lastname: Dkhil
authors.forename: H
authors.initials: H
authors.lastname: Karoui
authors.forename: M
authors.initials: M
authors.lastname: El Ayeb
mesh_terms: D000595:Amino Acid Sequence; D002850:Chromatography, Gel; D019483:Disintegrins / Q000737:chemistry* / Q000302:isolation & purification; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000302:isolation & purification; D016415:Sequence Alignment; D014757:Viper Venoms / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D019483:Disintegrins; D010975:Platelet Aggregation Inhibitors; D014757:Viper Venoms; C428664:lebein