A main part of eukaryotic proteins is modified after translation. One of these posttranslational modifications is the intramolecular cyclisation of glutaminyl- or glutamyl-residues at the N-terminus of peptides or proteins forming pyroglutamate (pE). This pE-residue increases stability against proteolytic degradation by aminopeptidases and/or mediates specific interaction of animal peptides/proteins. pE-formation is catalyzed by the enzyme glutaminyl cyclase (QC). The first tertiary structure of an invertebrate QC (D. melanogaster) and a mitochondrial localized QC was analyzed by X-ray crystallography in this work. In addition, posttranslational modifications of secreted QCs were shown as well. Furthermore, in the interaction with the potent QC-inhibitor PBD150 potential involved regions of the enzyme have been identified and contribution to ligand interaction was assessed by mutational analysis. The gained data are applied to evaluate binding modes of further QC inhibitors.