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

(master student) investigate whether alternative covalent modifications in the 8�-position are
feasible, i.e. whether aspartate or tyrosine can form a covalent bond to the 8�-methyl group.
In collaboration with Prof. Toni Kutchan at the Donald Danforth Plant Science Center in St.
Louis, we have identified other plant genes that apparently encode flavin-dependent oxidases.
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. Previously, 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 yeast
protein. This work revealed that yeast DPPIII features a novel protein topology.
Structure of human DPPIII in its open form (right) and peptide liganded (closed) form
In collaboration with a structural genomics group in Toronto led by Dr. Sirano Dhe-Paganon,
Gustavo Arruda (PhD student in Karl Gruber’s group) solved the structure of the human
enzyme both in its open (right, above) and closed conformation (left, above). The latter
structure was obtained by co-crystallization of an inactive variant of human DPPIII with a
tightly bound peptide. These two new structures constitute a major breakthrough in our effort
to understand the physiological role of the enzyme and pave the way for the development of
8