| Abstract: | The dipeptidyl peptidase (DPP) family members, including DPP-IV, DPP8, DPP9 and others, cleave the peptide bond after the penultimate proline residue and are drug target rich. The dimerization of DPP-IV is required for its activity. A propeller loop located at the dimer interface is highly conserved within the family. Here we carried out site-directed mutagenesis on the loop of DPPIV and identified several residues important for dimer formation and enzymatic activity. Interestingly, the corresponding residues on DPP9 have a different impact whereby the mutations decrease activity without changing dimerization. Thus the propeller loop seems to play a varying role in different DPPs. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: DPP-IV and DPP-IVphysically interact by comigration in gel electrophoresis (View interaction: 1, 2, 3, 4) DPP9 and DPP9bind by circular dichroism (View interaction) DPP-IV and DPP-IVbind by circular dichroism (View interaction: 1, 2, 3, 4, 5) DPP-IV and DPP-IVbind by cosedimentation in solution (View interaction: 1, 2, 3, 4, 5) ADAbinds to DPP-IV by surface plasmon resonance (View interaction: 1, 2, 3, 4, 5, 6) DPP9 and DPP9bind by cosedimentation in solution (View interaction). |
