Fig. 4: Allosteric small-molecule activator compound 3 induces ERAP1 closure.

a Preferred binding pose for compound 3 at an interdomain interface distal to the active site20. b Compound 3 activates hydrolysis of dipeptide substrate leucine-amidomethylcoumarin (Leu-AMC). c–e ERAP1 adopts closed conformation in the presence of compound 3, as measured by (c) Rg analysis, and (d) fitting to MD models. e Residual plot of best structural model fit to SAXS data in the presence of compound 3, with crystal structure model fits shown for reference. Each data point in (c) represents a single independent experiment with n = 1 and the error of linear fit for each independent experiment is shown as error bars. Source data are provided as a Source Data file.