Investigation of the Structural Metal Dependency of P. falciparum Arginase with Molecular Dynamics

Arginase (L-arginine-urea hydrolase, EC 3.5.3.1) catalyses the hydrolysis of (L-)arginine to (L-)ornithine and urea (Fig. 2.1). The arginase fold also includes agmatinase (Ouzounis and Kyrpides, 1994; Ahn et al., 2004) which converts agmatine to putrescine and urea. Agmatine is formed by decarboxylation of arginine (arginine decarboxylase). Arginase is thus part of one of two alternative biosynthetic routes to putrescine (Fig. 1.2). Arginase and agmatinase form part of the ureohydrolase superfamily, that also includes histone de-acetylase and acetylpolyamine amidohydrolase (Dowling et al., 2008). This superfamily is considered to be a very ancient fold that was probably present in the last universal common ancestor (Ouzounis et al., 2006). Arginase is thought to have evolved later from the agmatinase fold since the presence of ornithine early in evolution may have been detrimental due to mis-incorporation into proteins (Sekowska et al., 2000).