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Bacterial Multidrug Exporters pp 37–57Cite as

Crystallographic Analysis of MATE-Type Multidrug Exporter with Its Inhibitors

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1700))

Abstract

Multidrug exporters expressed in pathogens efflux substrate drugs such as antibiotics, and thus, the development of inhibitors against them has eagerly been anticipated. Furthermore, the crystal structures of multidrug exporters with their inhibitors provide novel insights into the inhibitory mechanism and the development of more specific and effective inhibitors. We previously reported the complex structures of the Multidrug And Toxic compound Extrusion (MATE)-type multidrug exporter with the macrocyclic peptides, which inhibit the efflux of substrates by the MATE-type multidrug exporter (Tanaka et al., Nature 496:247–251, 2013). In this chapter, we describe methodologies of the screening and synthesis of macrocyclic peptides as inhibitors, as well as the purification, crystallization, and structure determination of the complexes of the MATE-type multidrug exporter with its inhibitors.

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Author information

Authors and Affiliations

  1. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan

    Tsukasa Kusakizako & Osamu Nureki

  2. Department of Systems Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5, Takayama-cho, Ikoma, Nara, 630-0192, Japan

    Yoshiki Tanaka

  3. Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Christopher J. Hipolito & Hiroaki Suga

  4. Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan

    Christopher J. Hipolito

Authors
  1. Tsukasa Kusakizako
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  2. Yoshiki Tanaka
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  3. Christopher J. Hipolito
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  4. Hiroaki Suga
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  5. Osamu Nureki
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Corresponding author

Correspondence to Osamu Nureki .

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Editors and Affiliations

  1. Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan

    Akihito Yamaguchi

  2. Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan

    Kunihiko Nishino

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Kusakizako, T., Tanaka, Y., Hipolito, C.J., Suga, H., Nureki, O. (2018). Crystallographic Analysis of MATE-Type Multidrug Exporter with Its Inhibitors. In: Yamaguchi, A., Nishino, K. (eds) Bacterial Multidrug Exporters. Methods in Molecular Biology, vol 1700. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7454-2_3

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  • DOI: https://doi.org/10.1007/978-1-4939-7454-2_3

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7452-8

  • Online ISBN: 978-1-4939-7454-2

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