Fig. 1: An inhibitor 11-2F of PRMT5 exhibits positive cooperativity with MTA.

a Dose-dependent inhibition of enzyme activity by 11-2F. IC50 ~730 nM. The chemical structure of 11-2F is showed on the right. Errors: s.d., n = 3. b SPR of 11-2F binding and unbinding to PRMT5:MEP50 in the absence of MTA, leading to a calculated KD ~13.6 μM. c SPR of 11-2F interaction with the enzyme in the presence of MTA. KD ~82 nM. The apparent positive coupling coefficient between 11-2F and MTA is ~166. d, e SPR of 11-2F binding to PRMT5:MEP50 complex in the presence of SAH (d) and SAM (e), showing much weaker affinity, 1.6 and 0.38 μM, respectively, and thus much weaker synergy than MTA.