NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir

► Protease (PR) of XMR virus (XMRV) was successfully synthesized with cell-free system. ► Interface of XMRV PR with an inhibitor, amprenavir (APV), was identified with NMR. ► Structural heterogeneity is induced for two PR protomers in the APV:PR = 1:2 complex. ► Structural heterogeneity is transmitted even to distant regions from the interface. ► Long-range transmission of structural change may be utilized for drug discovery.