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Methods Mol Biol. 2018;1700:37-57. doi: 10.1007/978-1-4939-7454-2_3.

Crystallographic Analysis of MATE-Type Multidrug Exporter with Its Inhibitors.

Author information

1
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
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.
3
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
4
Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
5
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan. nureki@bs.s.u-tokyo.ac.jp.

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.

KEYWORDS:

Inhibitors; Macrocyclic peptide; Membrane proteins; Multidrug exporter; Multidrug resistance; RaPID system; Structural analysis; Transporter; X-ray crystallography

PMID:
29177824
DOI:
10.1007/978-1-4939-7454-2_3
[Indexed for MEDLINE]

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