Staff Members of the Institute of Biochemistry, TU - Institut für ...

currently expressed in our laboratory in order to characterize the role of the enzymes in
alkaloid biosynthesis (thesis project of Silvia Wallner).
Dipeptidylpeptidase III
Dipeptidyl-peptidases III (DPPIII; EC 3.4.14.4) are Zn-dependent enzymes with molecular
masses of ca. 80-85 kDa that specifically cleave the first two amino acids from the Nterminus
of different length peptides. All known DPPIII sequences contain the unique motif
HEXXGH, which enabled the recognition of the dipeptidyl-peptidase III family as a distinct
evolutionary metallopeptidase family (M49). In mammals, DPPIII is associated with
important physiological functions such as pain regulation, and hence the enzyme is a potential
drug target. Sigrid Deller and Nina Jajcanin-Jozic have successfully expressed, purified and
characterized the recombinant yeast enzyme, and Pravas Baral in Karl Gruber’s laboratory at
the Karl-Franzens-University has elucidated the crystal structure of the protein. This work
revealed that yeast DPPIII is the first representative of a novel protein topology:
We are now focusing on structures with potential substrates or inhibitors bound in the active site.
Towards that goal, we are generating inactive mutant proteins to enable cocrystallisation with
peptide substrates. In addition, we have produced recombinant human DPPIII and are in the
process to determine the crystal structure to provide the basis for the development of potentially
useful inhibitors of the enzyme (Gustavo Arruda’s thesis project in Prof. Gruber’s laboratory
supported by Alexandra Binter).
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