Seibutsu Butsuri
Online ISSN : 1347-4219
Print ISSN : 0582-4052
ISSN-L : 0582-4052
Volume 56 , Issue 6
Issue 328
Showing 1-15 articles out of 15 articles from the selected issue
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  • Tomohiro YAMAGUCHI, Hiroaki KATO
    2016 Volume 56 Issue 6 Pages 315-318
    Published: 2016
    Released: November 29, 2016
    JOURNALS FREE ACCESS

    P-glycoprotein (P-gp) is an ATP-binding cassette (ABC) transporter that transports various substrates from the cells. So far, crystal structures of several transporters structurally similar to P-gp have been reported. However, the multidrug transport mechanism of P-gp remains unclear, because their resolutions are low or the transporters have different functions from P-gp. Recently, we determined the crystal structures of the structural and functional homolog of P-gp, CmABCB1, from Cyanidioschyzon merolae at 2.4 Å resolution. Based on the structural comparison between CmABCB1 and the other ABC transporters, we explain structural features conserved in the true P-gp homologs, but unconserved in the other structurally similar ones.

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  • Jun-ichi OKADA
    2016 Volume 56 Issue 6 Pages 319-323
    Published: 2016
    Released: November 29, 2016
    JOURNALS FREE ACCESS

    We developed a novel cardiotoxicity testing system combining in vitro channel assays and a three-dimensional heart simulator. The inhibitory effects of drugs were measured for the six ion channels using the automated patch clamp technique. According to the dose-inhibition relations thus obtained, effects of drugs under various plasma concentrations were reproduced by changing parameters values of 22 million cell models implemented in the heart simulator. This system can predict drug-induced proarrhythmic risk more accurately compared with the currently used methods such as the QT interval and the hERG test.

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