Role of a propeller loop in the quaternary structure and enzymatic activity of prolyl dipeptidases DPP-IV and DPP9

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-IV physically interact by comigration in gel electrophoresis (View interaction: 1 , 2 , 3 , 4 ) DPP9 and DPP9 bind by circular dichroism ( View interaction ) DPP-IV and DPP-IV bind by circular dichroism (View interaction: 1 , 2 , 3 , 4 , 5 ) DPP-IV and DPP-IV bind by cosedimentation in solution (View interaction: 1 , 2 , 3 , 4 , 5 ) ADA binds to DPP-IV by surface plasmon resonance (View interaction: 1 , 2 , 3 , 4 , 5 , 6 ) DPP9 and DPP9 bind by cosedimentation in solution ( View interaction )