The co-crystal structure of beta-phenethylamine fragment inhibitor 5 bound to DPP-IV revealed that the phenyl ring occupied the proline pocket of the enzyme. This finding provided the basis for a general hypothesis of a reverse binding mode for beta-phenethylamine-based DPP-IV inhibitors. Novel inhibitor design concepts that obviate substrate-like structure-activity relationships (SAR) were thereby enabled, and novel, potent inhibitors were discovered.
Representative scheme of DPP4N_Peptidase_S9 structure and an image from PDBsum server
no Image
Databases
PDB-Sum
2BUC Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
2BUCFold classification based on Structure-Structure alignment of Proteins - FSSP server
