Identification of an Additional Metal-Binding Site in Human Dipeptidyl Peptidase III

Dipeptidyl peptidase III (DPP III, EC 3.4.14.4) is a monozinc metalloexopeptidase that hydrolyzes dipeptides from the N-terminus of peptides consisting three or more amino acids. Recently, DPP has attracted great interest scientists, and numerous studies have been conducted showing it involved in regulation various physiological processes. Since only metalloenzyme among dipeptidyl peptidases, we considered important to study process binding exchange physiologically relevant metal dications III. Using fluorimetry, measured Kd values for Zn2+, Cu2+, Co2+ catalytic site, using isothermal titration calorimetry (ITC), these metals an additional site. The structure metal’s site known previous studies, this work, affinities were calculated Co2+, Mn2+ QM approach. structures sites Zn2+ Cu2+ also identified, MD simulations showed two ions bound inhibitory exchanged less frequently than sites.