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Intrinsic interaction mode of an inhalation anesthetic with globular proteins: a comparative study on ligand recognition

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Abstract

Interaction mode of an inhalation anesthetic halothane with water-soluble globular proteins, myoglobin (Mgb) and lysozyme (Lys), was studied by differential scanning calorimetry (DSC) and viscometry, and the results were compared with those of bovine serum albumin (BSA). The anesthetic sensitivity was markedly different among the proteins: Mgb was destabilized, Lys was slightly destabilized, and BSA was conversely stabilized. Further, the interaction mode was quite different from those of specific binders for the proteins. The anesthetic sensitivity was highly correlated with the hydrophilicity on the protein surface (Mgb < Lys < BSA) and the rigidity of the protein structure (BSA ≈ Mgb < Lys). We showed that the anesthetic sensitivity among globular proteins can be roughly classified into four categories, and proteins with small hydrophilicity and soft structure are suitable as model proteins of anesthesia. By contrast, the binding of the specific binders was characterized by the lower effective concentrations. The molar ratio of the binder to the protein at the effective concentration was well consistent with the binding number determined from the X-ray structural analysis. Moreover, the interaction mode of the binder was not necessarily in accord with the mode expected from the change in the protein structure. Considering the above facts, we can systematically interpret the effect of an anesthetic on globular proteins by four factors: (1) hydrophobicity of an anesthetic, (2) hydrophilicity of a protein surface, (3) rigidity of a protein structure, and (4) molar ratio of an anesthetic to a protein at the effective concentration.

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Acknowledgement

The authors all thank the late Professor Issaku Ueda at University of Utah for his encouragement and suggestions for researches of the molecular mechanism of anesthesia.

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  1. Makoto Nishimoto

    Present address: Department of Material Science, Wakayama National College of Technology, 77 Nada, Noshima, Gobo, Wakayama, 644-0023, Japan

Authors and Affiliations

  1. Department of Life System, Institute of Technology and Science, The University of Tokushima, 2-1 Minamijosanjima-cho, Tokushima, 770-8506, Japan

    Makoto Nishimoto, Nobutake Tamai, Shoji Kaneshina & Hitoshi Matsuki

  2. Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, 2-1 Minamijosanjima-cho, Tokushima, 770-8506, Japan

    Ukyo Komatsu

  3. Department of Chemistry, Faculty of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan

    Michio Yamanaka

  4. Division of Anesthesia and Emergency Medicine, Kaisei General Hospital, 3-5-28 Muro-machi, Sakaide, Kagawa, 762-0007, Japan

    Kenji Ogli

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  1. Makoto Nishimoto
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Correspondence to Hitoshi Matsuki.

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Nishimoto, M., Komatsu, U., Tamai, N. et al. Intrinsic interaction mode of an inhalation anesthetic with globular proteins: a comparative study on ligand recognition. Colloid Polym Sci 289, 1785–1797 (2011). https://doi.org/10.1007/s00396-011-2491-z

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  • DOI: https://doi.org/10.1007/s00396-011-2491-z

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