Arginase Structure and Inhibition: Catalytic Site Plasticity Reveals New Modulation Possibilities.

ABSTRACT: Metalloenzyme arginase is a therapeutically relevant target associated with tumor growth. To fight cancer immunosuppression, arginase activity can be modulated by small chemical inhibitors binding to its catalytic center. To better understand molecular mechanisms of arginase inhibition, a careful computer-aided mechanistic structural investigation of this enzyme was conducted. Using molecular dynamics (MD) simulations in the microsecond range, key regions of the protein active site were identified and their flexibility was evaluated and compared. A cavity opening phenomenon was observed, involving three loops directly interacting with all known ligands, while metal coordinating regions remained motionless. A novel dynamic 3D pharmacophore analysis method termed dynophores has been develope

SUBMITTER: Mortier J 

PROVIDER: S-EPMC5648838 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature