title: Two highly conserved glutamic acid residues in the predicted beta propeller domain of dipeptidyl peptidase IV are required for its enzyme activity.
abstract: Dipeptidyl peptidase IV (DPP IV) is a member of the prolyl oligopeptidase family and modifies the biological activities of certain chemokines and neuropeptides by cleaving their N-terminal dipeptides. This paper reports the identification 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 beta 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 suggests a novel role in proteolysis for residues of DPP IV distant from the Ser-Asp-His catalytic triad.
authors.affiliation: A.W. Morrow Gastroenterology and Liver Centre, Centenary Institute of Cell Biology and Cancer Medicine, Royal Prince Alfred Hospital and the University of Sydney, Newton, NSW, Australia. c.abbott@centenary.usyd.edu.au
authors.forename: C A
authors.initials: CA
authors.lastname: Abbott
authors.forename: G W
authors.initials: GW
authors.lastname: McCaughan
authors.forename: M D
authors.initials: MD
authors.lastname: Gorrell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D017124:Conserved Sequence; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry* / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D017354:Point Mutation; D000085822:Prolyl Oligopeptidases; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics; D013379:Substrate Specificity; D014162:Transfection
chemical_list: D018698:Glutamic Acid; D018819:Dipeptidyl Peptidase 4; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases