3.A.1.201.21
Half sized ABCB1 drug (verapamil; rhodamine 6G) exporter of specificity similar to that of P-glycoprotein (3.A.1.201.1).  The 3-d structures of the unbound (2.6 Å) and the allosteric inhibitor-bound (2.4 Å) forms have been determined (Kodan et al. 2014).  The outward opening motion is required for ATP hydrolysis. Kodan et al. 2019 have reported a pair of structures of this homodimeric P-glycoprotein: an outward-facing conformational state with bound nucleotide, and an inward-facing apo state, at resolutions of 1.9 Å and 3.0 Å, respectively. Features that can be clearly visualized include ATP binding with octahedral coordination of Mg²⁺; an inner chamber that significantly changes in volume with the aid of tight connections among TMSs 1, 3, and 6; a glutamate-arginine interaction that stabilizes the outward-facing conformation; and extensive interactions between TMS1 and TMS3, a property that distinguishes multidrug transporters from floppases (Kodan et al. 2019). The crystal structure of the CmABCB1 G132V mutant, which favors the outward-facing state, reveals the mechanism of the pivotal joint between TMS1 and TMS3 (Matsuoka et al. 2021). The crystal structure of this CmABCB1 multi-drug exporter in lipidic mesophase has been revealed by LCP-SFX, suggesting flexibility of the substrate exit region of the protein (Pan et al. 2022).  Structure-based alteration of tryptophan residues of CmABCB1 allows assessment of substrate binding using fluorescence spectroscopy (Inoue et al. 2022).