Protein Origami

Pharmacological rescue of mutant GnRHRs. Loci of fourteen reported point mutations of the human GnRHR (N¹⁰K, T³²I, E⁹⁰K, Q¹⁰⁶R, A¹²⁹D, R¹³⁹H, S¹⁶⁸R, C²⁰⁰Y, S²¹⁷R, R²⁶²Q, L²⁶⁶R, C²⁷⁹Y, Y²⁸⁴C, and L³¹⁴X) isolated from patients with hypogonadotropic hypogonadism, of which eleven were rescued with IN3. The two internal substitutions that cannot be rescued by IN3 are less than 20 angstroms apart; the red circle represents the site of truncation of the C-terminal deletion mutant. The range of loci of mutation from which rescue can be effected is remarkably broad.