Crystal structures of a bacterial dipeptidyl peptidase IV reveal a novel substrate recognition mechanism distinct from that of mammalian orthologues.

摘要: Dipeptidyl peptidase IV (DPP IV, DPP4, or DAP IV) preferentially cleaves substrate peptides with Pro Ala at the P1 position. The recognition mechanism has been fully elucidated for mammalian DPP by crystal structure analyses but not bacterial orthologues. Here, we report structures of a (PmDAP in its free form and complexes two kinds dipeptides as well non-peptidyl inhibitor 1.90 to 2.47 A resolution. Acyl-enzyme intermediates were observed dipeptide PmDAP whereas tetrahedral reported oligopeptide IVs. This variation reflects different structural environments active site Arg residues, which are involved carbonyl group, enzymes. A phylogenetic analysis revealed that is closer relative dipeptidyl peptidases 8 9 (DPP8 DPP9, IV-family enzymes) than IV. These results provide new insights into IVs may assist development selective inhibitors from pathogenic asaccharolytic bacteria, utilise proteins an energy source.