Structural insights into human Arginase-1 pH dependence and its inhibition by the small molecule inhibitor CB-1158.

Arginase-1 is a manganese-dependent metalloenzyme that catalyzes the hydrolysis of L-arginine into L-ornithine and urea. Arginase-1 is abundantly expressed by tumor-infiltrating myeloid cells that promote tumor immunosuppression, which is relieved by inhibition of Arginase-1. We have characterized the potencies of the Arginase-1 reference inhibitors (2)-2-amino-6-boronohexanoic acid (ABH) and -hydroxy-nor-L-arginine (nor-NOHA), and studied their pH-dependence and binding kinetics.