Examining Arginase-1 Trimerization Uncovers a Promising Allosteric Site for Inhibition

Arginase-1 (ARG-1) is a promising target for cancer immunotherapy, but the small size and the highly polar nature of its catalytic site present significant challenges for inhibitor development. An alternative strategy to induce enzyme inhibition by targeting protein oligomerization has been developed recently, offering several advantages such as increased selectivity, promotion of protein degradation, and potential substoichiometric inhibition. In this study, we demonstrated that only trimeric ARG-1 is active, which was confirmed by producing monomeric arginase-1. Through