Arginase structure

Christianson, D. W. (2005). Arginase structure, mechanism, and physiological role in male and female sexual arousal. Accounts of Chemical Research, 38, 191—201. 

We begin this overview of manganese biochemistry with a brief account of its role in the detoxification of free radicals, before considering the function of a dinuclear Mn(II) active site in the important eukaryotic urea cycle enzyme arginase. We then pass in review a few microbial Mn-containing enzymes involved in intermediary metabolism, and conclude with the very exciting recent results on the structure and function of the catalytic manganese cluster involved in the photosynthetic oxidation of water. 

Arginine is capable of binding in the active site of PAH but it is not an enzyme substrate. Crystal structures of PAH from Streptomyces clavuligerus show that the metal binding site is very similar to that of arginase and the Mn—Mn distance is 3.3 A The main difference between arginase and PAH is in the binding pocket at the o-amino-terminus of the substrate. ... 

Arginase (EC 3.5.3.T) mediates the hydrolytic cleavage of L-canavanine to produce L-canaline and urea. L-Canaline, 2-amino-4-aminooxybutyric acid, bears the same structural analogy to L-ornithine as canavanine does to arginine. The aminooxy group of canaline with its pK value of 3.96 differs markedly from the 6-amino function of ornithine (pK = 10.76). 

The 2.8 A resolution crystal structure of the arginase from the thermophilic bacterium Bacillus caldevelox [112] reveals a hexameric structure with at least one Mn2+ bound per subunit. The 2.1 A resolution structure of rat liver arginase, reported recently [81], reveals it to be trimeric, with the overall fold of the arginase monomer belonging to the a/p protein class. The Mn"Mnn aggregate, shown in Figure 24, is found at the bottom of a 15 A active-site cleft. 

Kanyo ZF, Scolnick LR, Ash DE, Christianson DW. Structure of a unique binuclear manganese cluster in arginase. Nature 1996 383 554-7. 

Muller, I. B., Walter, R. D., and Wrenger, C. (2005). Structural metal dependency of the arginase from the human malaria parasite Plasmodium falciparum. Biol. Chem. 386,117-126. 

One particularly key metallohydrolase that contains manganese is the enzyme arginase (4-7), an enzyme for which a crystal structure... 

Fig. 1. Structure of the active site of the rat liver arginase enzyme based on (S).

The biological applications of manganese are numerous and quite varied. Although most of these biological roles utilize manganese in structural or hydrolytic systems, some very striking redox systems are also known. The hydrolytic roles are, of course, not to be overlooked with respect to the widespread and critical arginase enzyme, which exhibits a strict requirement for two Mn" ions. The ribo-nuclease hydrolases of retroviral reverse transcriptase are another key nonredox application—for example, the ribonuclease hydrolase from HIV-1. 

The official EC name of this enzyme is L-arginine amidinohydrolase the last word refers to the fact that the amidino group (the three-nitrogen group at the top of the structure above) is cleaved from arginine by the introduction of a water molecule across the C—N bond. In a reaction, a nonpeptide C—N bond is cleaved thus, the second EC number for arginase is 5. Its whole EC number is 3.5.3.1. 

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