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Structural and dynamical properties of KTS-disintegrins: A comparison between Obtustatin and Lebestatin

Authors

  • Isabella Daidone,

    Corresponding author
    1. Department of Physical and Chemical Sciences, University of L'Aquila, via Vetoio (Coppito 1), 67010 L'Aquila, Italy
    • Department of Physical and Chemical Sciences, University of L'Aquila, via Vetoio (Coppito 1), 67010 L'Aquila, Italy
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  • Massimiliano Aschi,

    1. Department of Physical and Chemical Sciences, University of L'Aquila, via Vetoio (Coppito 1), 67010 L'Aquila, Italy
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  • Maria Patamia,

    1. Institute of Biochemistry and Clinical Biochemistry, Catholic University and Institute for the Chemistry of Molecular Recognition, CNR, Largo F. Vito 1, 00168 Rome, Italy
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  • Argante Bozzi,

    1. Department of Biomedical Sciences and Technologies, University of L'Aquila, via Vetoio (Coppito 2), 67010 L'Aquila, Italy
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  • Raffaele Petruzzelli

    1. Department of Biomedical Sciences,“G. D'Annunzio” University, Via dei Vestini 29, 66013 Chieti, Italy
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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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 21KTS23 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. © 2012 Wiley Periodicals, Inc.

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