title: Relating structure to function in the beta-propeller domain of dipeptidyl peptidase IV. Point mutations that influence adenosine deaminase binding, antibody binding and enzyme activity.
abstract: Point mutations in human CD26/DP IV were analysed for adenosine deaminase (ADA) binding, monoclonal antibody (mAb) binding and DP IV enzyme activity. Point mutations at either Leu294 or Val341 ablated ADA binding. Binding by mAbs that inhibit ADA binding was found to involve both Leu340 to Arg343 and Thr440/Lys441. Glu205 and Glu206 were found to be essential for enzyme activity. All residues of interest were mapped onto a model of the beta-propeller domain of DP IV. These data led us to suggest that in DP IV and related peptidases ligand and antibody binding sites are non-linear and that enzyme activity depends on charged sidechains that surround the entrance to the central tunnel of the beta-propeller.
authors.affiliation: A.W. Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, NSW, Australia.
authors.forename: M D
authors.initials: MD
authors.lastname: Gorrell
authors.forename: C A
authors.initials: CA
authors.lastname: Abbott
authors.forename: T
authors.initials: T
authors.lastname: Kähne
authors.forename: M T
authors.initials: MT
authors.lastname: Levy
authors.forename: W B
authors.initials: WB
authors.lastname: Church
authors.forename: G W
authors.initials: GW
authors.lastname: McCaughan
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D019556:COS Cells; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D019151:Peptide Library; D017354:Point Mutation; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D019151:Peptide Library; D018819:Dipeptidyl Peptidase 4