►Two isoforms in humans Arginase1 (Arg 1, cytosol), Arginase 2 (Arg2 mitochondria)
►Both catalyze the hydrolysis of L arginine to L ornithine and urea through a mechanism involving one hydroxide and two manganese ions
►Implicated in cancer immunosuppression and cancer tumor growth: an increased metabolism of L Arg by myeloid derived suppressor cells producing Arg 1 inhibits T lymphocyte response
►Other TIs include the following asthma, erectile dysfunction, cystic fibrosis, and atherosclerosis
►A strong binder is required to displace the hydroxide and replace it in the manganese coordination network
►X Ray structures of arginase cavity indicate a small volume, allowing little structural diversity
between the metal coordinating and the amino acid moiety of the ligand
►Almost all the published Arg inhibitors exhibit insufficient differences in affinity to provide isoform
selective inhibition in cultured cells or in vivo
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