Structural and dynamical properties of KTS‐disintegrins: A comparison between Obtustatin and Lebestatin |
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| Authors: | Isabella Daidone Massimiliano Aschi Maria Patamia Argante Bozzi Raffaele Petruzzelli |
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| Affiliation: | 1. Department of Physical and Chemical Sciences, University of L'Aquila, via Vetoio (Coppito 1), 67010 L'Aquila, Italy;2. Institute of Biochemistry and Clinical Biochemistry, Catholic University and Institute for the Chemistry of Molecular Recognition, CNR, Largo F. Vito 1, 00168 Rome, Italy;3. Department of Biomedical Sciences and Technologies, University of L'Aquila, via Vetoio (Coppito 2), 67010 L'Aquila, Italy;4. Department of Biomedical Sciences,“G. D'Annunzio” University, Via dei Vestini 29, 66013 Chieti, Italy |
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| 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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| Keywords: | molecular dynamics simulations peptides essential dynamics binding |
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