Fig. 2: Structure of human TRPV1 in complex with the inhibitor SB-366791.
From: Human TRPV1 structure and inhibition by the analgesic SB-366791
a Exemplar whole-cell current recorded at –40 mV from HEK 293 cell expressing hTRPV1 in response to application of 1 µM of capsaicin (Cap) and 10 µM of SB-366791. b Quantification of the inhibitory effect of 10 µM SB-366791 on hTRPV1 peak current amplitude in the presence of 1 µM capsaicin, measured 10 s after SB-366791 application. Statistical analysis: two-tailed paired t-test. ***P = 0.0003. Data points represent paired recordings from 5 individual cells. c Quantification of capsaicin-stimulated hTRPV1 peak current amplitude recovery after termination of SB-366791 application. The cell was washed for at least 2 min before the second application of Cap. Data are shown as mean ± SEM. Data points represent recordings from 5 individual cells. d, e hTRPV1SB-366791 structure viewed parallel to the membrane (d) or extracellularly (e), with subunits colored green, yellow, pink, and blue, and lipids shown as purple sticks. f Chemical structure (left) and molecular model (right) of SB-366791, with the cryo-EM density for the inhibitor shown as red mesh. g Close-up view of the binding pocket, with SB-366791 and residues that contribute to its binding shown in sticks. h Exemplar whole-cell currents recorded from hTRPV1-expressing HEK 293 cell in response to a voltage ramp in the presence of different concentrations of SB-366791 at pH 5. i Concentration-dependencies of SB-366791 inhibition of wild-type and mutant hTRPV1 channels at pH 5, measured at +80 mV and normalized to the value of pH5-induced current. Data are shown as mean ± SEM. Lines represent fits to the Hill equation (WT, n = 7; Y511A, n = 7) or connect data points (L515A, n = 7; L547R, n = 7, T550A, n = 7). Source data are provided as a Source Data file.
