title: Structural and dynamical properties of KTS-disintegrins: A comparison between Obtustatin and Lebestatin.
abstract: Obtustatin and Lebestatin are lysine-threonine-serine (KTS)-disintegrins, which are a family of low molecular weight polypeptides present in many viperidae venoms and are potent and specific inhibitors of collagen-binding integrins. The integrin binding loop, harboring the (21)KTS(23) motif, and the C-terminal tail are known to be responsible for the selective binding to the α1β1 integrin. Despite a very high sequence homology (only two mutations are present in Lebestatin relative to Obtustatin, namely R24L and S38L), Lebestatin exhibits a higher inhibitory effect than Obtustatin on cell adhesion and cell migration to collagens I and IV. Here we show, by means of molecular dynamics simulations of the two polypeptides in aqueous solution, that Lebestatin possesses a higher flexibility of the C-terminal tail and a greater solvent accessibility of the integrin binding loop than Obtustatin. It may be hypothesized that these properties may contribute to the higher binding-affinity of Lebestatin to its biological partner.
authors.affiliation: Department of Physical and Chemical Sciences, University of L'Aquila, via Vetoio (Coppito 1), 67010 L'Aquila, Italy. daidone@caspur.it.
authors.forename: Isabella
authors.initials: I
authors.lastname: Daidone
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Aschi
authors.forename: Maria
authors.initials: M
authors.lastname: Patamia
authors.forename: Argante
authors.initials: A
authors.lastname: Bozzi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Petruzzelli
mesh_terms: D000818:Animals; D019483:Disintegrins / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D012694:Serine / Q000737:chemistry; D013912:Threonine / Q000737:chemistry; D014757:Viper Venoms / Q000737:chemistry*; D017819:Viperidae
chemical_list: D019483:Disintegrins; D014757:Viper Venoms; C000606729:lebestatin protein, Macrovipera lebetina; C474313:obtustatin, Vipera lebetina obtusa; D013912:Threonine; D012694:Serine; D008239:Lysine