Crystallization of an apo form of human arginase: using all the tools in the toolbox simultaneously.

Arginase (EC 3.5.3.1) is an aminohydrolase that acts on L-arginine to produce urea and ornithine. Two isotypes of the enzyme are found in humans. Type I is predominantly produced in the liver and is a homotrimer of 35†kDa subunits. Human arginase (hArginase) I is seen to be up-regulated in many diseases and is a potential therapeutic target for many diverse indications. Previous reports of crystallization and structure determination of hArginase have always included inhibitors of the enzyme: here, the first case of a true apo crystal form of the enzyme which is suitable for small-molecule soaking is reported. The crystals belonged to space group P2(1)2(1)2(1) and have approximate unit-cell parameters a=53, b=67.5, c=250†à . The crystals showed slightly anisotropic diffraction to beyond 2.0†à resolution.