Dipeptidyl peptidase 8 and 9: specificity and molecular characterization compared to dipeptidyl peptidase IV

Jais R. Bjelke , Jesper Christensen , Per F. Nielsen , Sven Branner , Anders B. Kanstrup , Nicolai Wagtmann , Hanne B. Rasmussen (1)

1 Protein Structure and Biophysics

Dipeptidyl peptidases 8 and 9 have been identified as gene members of the S9b family of dipeptidyl peptidases. Here we report the characterization of recombinant dipeptidyl peptidase 8 and 9 using the baculovirus expression system. We have found that only full-length variants of the two proteins can be expressed as active peptidases of 882 and 892 amino acids for dipeptidyl peptidase 8 and 9, respectively. We further show that the purified proteins are active dimers and that they show similar Michaelis-Menten kinetics and substrate specificity. Both cleave the peptide hormones glucagon-like peptide-1, glucagon-like peptide-2, neuropeptide Y and peptide YY with marked kinetic differences compared to dipeptidyl peptidase IV. Inhibition of dipeptidyl peptidase IV, dipeptidyl peptidase 8 and 9 using the well-known dipeptidyl peptidase IV inhibitor valine pyrrolidide resulted in similar Ki values, indicating that this inhibitor is nonselective for any of the three dipeptidyl peptidases.

Mots clés: Life Sciences

Jais R. Bjelke, Jesper Christensen, Per F. Nielsen, Sven Branner, Anders B. Kanstrup, et al.. Dipeptidyl peptidase 8 and 9: specificity and molecular characterization compared to dipeptidyl peptidase IV. Biochemical Journal, 2006, 396 (2), pp.391-399. ⟨10.1042/BJ20060079⟩. ⟨hal-00478513⟩