RecA protein and its homologs promote strand exchange of long DNA for homologous recombination, and are thus involved in repair and reorganization of DNA. The reaction occurs in a long filament formed by assembly of hundreds of RecA on a long DNA. This makes analysis very difficult. Still we start to understand how RecA recognizes sequence homology, how RecA finds the homologous part so quickly and how RecA exchanges the DNA strands by gathering and developing various approaches including, kinetic, structural, single molecule observation and molecular simulation analyses.
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.
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.