Figure 4.

An inhibitory concentration of vinblastine binding to P-gp alters HDX-MS in different catalytic states. (A) Peptides that show significant HDX changes for vinblastine binding to nucleotide-free, pre-hydrolysis (AMPPNP), and post-hydrolysis (ATP/VO₄) states of P-gp relative to the drug-free states of the catalytic cycle, plotted on apo and ATP-bound structures (PDB IDs: 5KPI and 6C0V). (B) Top-down view from membrane into cytoplasm of NBDs and ICHs. (C) Sequence plot of the sum of changes in HDX across time points. See Figures S6 and S7 for individual peptide plots and sequence plots for each time point.