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Thermodynamics of calmodulin and tubulin binding to the vinca-alkaloid vinorelbine

  • Structural and Functional Analysis of Biopolymers and Their Complexes
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Abstract

Vinca-alkaloids, such as vinblastine, and some of their derivatives, for example vinorelbine, are widely used in clinical therapy of leukemia and several types of tumors. Their effects are associated with the disfunctioning of the mitotic spindle, which leads to mitosis blockage and a shutting down of the cell cycle. Their primary target is tubulin; however, recent research has shown that some of the vinca-alkaloids inhibit calmodulin binding to its targets. Vinca-alkaloids binding with other proteins could be responsible for their efficiency and neuroprotection. Here, we investigated the thermodynamics of vinorelbine interactions with calmodulin and tubulin. It was determined that, unlike the other vinca-alkaloids, both vinorelbine binding sites are located in the C-domain of calmodulin and they are characterized by association constants of 4.0 × 105 and 5.4 × 104 M−1. At the same time, the thermodynamics of vinorelbine binding to tubulin are not much different from that of other vinca-alkaloids. These results will allow us to get a better insight on the reaction mechanisms of vinca-alkaloids on a secondary protein target.

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Abbreviations

NAV:

navelbine

VLB:

vinblastine

CaM:

calmodulin

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 199911, Russia

    P. O. Tsvetkov, A. A. Kulikova & A. A. Makarov

  2. INSERM UMR 911, Aix-Marseille Université, Faculté de Pharmacie, CRO2 Marseille, France

    F. Devred & D. Lafitte

  3. A.N. Belozersky Institute of Physico-Chemical Biology, M.V. Lomonosov Moscow State University, Moscow, 119991, Russia

    E. Yu. Zernii

Authors
  1. P. O. Tsvetkov
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  2. A. A. Kulikova
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  3. F. Devred
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  4. E. Yu. Zernii
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  5. D. Lafitte
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  6. A. A. Makarov
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Corresponding author

Correspondence to P. O. Tsvetkov.

Additional information

Original Russian Text © F.O. Tsvetkov, A.A. Kulikova, F. Devred, E.Yu. Zernii, D. Lafitte, A.A. Makarov, 2011, published in Molekulyarnaya Biologiya, 2011, Vol. 45, No. 4, pp. 697–702.

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Tsvetkov, P.O., Kulikova, A.A., Devred, F. et al. Thermodynamics of calmodulin and tubulin binding to the vinca-alkaloid vinorelbine. Mol Biol 45, 641–646 (2011). https://doi.org/10.1134/S0026893311040108

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  • DOI: https://doi.org/10.1134/S0026893311040108

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