Soft–Soft interactions in the protein–protein recognition process: The K+ channel-charybdotoxin case

Authors

  • Felipe Aparicio,

    1. Departamento de Ciencias Naturales, División de Ciencias Naturales e Ingeniería, Universidad Autónoma Metropolitana Cuajimalpa, Av. Pedro Antonio de los Santos 84, San Miguel Chapultepec, México D.F. 11850, México
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  • Nelly González-Rivas,

    1. Centro Conjunto de Investigación en Química Sustentable UAEM-UNAM, Carretera Toluca-Atlacomulco Km 14.5, Unidad San Cayetano, Toluca, Estado de México, C. P. 50200, México
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  • Joel Ireta,

    1. Departamento de Química, División de Ciencias Básicas en Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, A.P. 55-534, México D.F. 09340, México
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  • Arturo Rojo,

    1. Departamento de Ciencias Naturales, División de Ciencias Naturales e Ingeniería, Universidad Autónoma Metropolitana Cuajimalpa, Av. Pedro Antonio de los Santos 84, San Miguel Chapultepec, México D.F. 11850, México
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  • Laura I. Escobar,

    1. Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, México D.F., México
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  • Andrés Cedillo,

    1. Departamento de Química, División de Ciencias Básicas en Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, A.P. 55-534, México D.F. 09340, México
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  • Marcelo Galván

    Corresponding author
    1. Departamento de Química, División de Ciencias Básicas en Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, A.P. 55-534, México D.F. 09340, México
    • Departamento de Química, División de Ciencias Básicas en Ingeniería, Universidad Autónoma Metropolitana-Iztapalapa, A.P. 55-534, México D.F. 09340, México
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    • Fax: (+52 55) 58 04 64 15


Abstract

Molecular recognition between peptide blockers and ionic channels is a complex process that involves many effects. To determine if the short-range charge transfer effects play a significant role in this interaction, a chemical reactivity analysis of charybdotoxin (ChTX) and six of its mutants was carried out using global and local reactivity indices. The results show that global softness correlates with the affinity of ChTX, and its mutants to the channel indicating that soft–soft interactions play a role in the recognition process between ChTX and a potassium channel. The analysis of the local reactivity indicates that the toxin as a whole can be seen as a complex polydentate ligand with several places to coordinate with the external vestibule of the pore of the potassium channels. The successful treatment of point mutations supports the idea of using this tool in the study of chemical reactivity in proteins, in a similar way as substituent effects in organic chemistry. © 2012 Wiley Periodicals, Inc.

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