Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity

Dipeptidyl peptidase IV (DPP IV) is a member of the prolyl oligopeptidase f amily and modifies the biological activities of certain chemokines and neur opeptides by cleaving their N-terminal dipeptides. This paper reports the i dentification and possible significance of a novel conserved sequence motif Asp-Trp-(Val/Ile/Leu)-Tyr-Glu-Glu-Glu (DW(V/I/L)YEEE) in the predicted bet a propeller domain of the DPP IV-like gene family. Single amino acid point mutations in this motif identified two glutamates, at positions 205 and 206 , as essential for the enzyme activity of human DPP IV. This observation su ggests a novel role in proteolysis for residues of DPP IV distant from the Ser-Asp-His catalytic triad. (C) 1999 Federation of European Biochemical So cieties.