InterPro domain: IPR006035

The ureohydrolase superfamily includes arginase ( 3.5.3.1 ), agmatinase ( 3.5.3.11 ), formiminoglutamase ( 3.5.3.8 ) and proclavaminate amidinohydrolase ( 3.5.3.22 ) [ 1 ]. These enzymes show trimeric or hexameric structures and share a 3-layer alpha-beta-alpha structure [ 2 , 2 , 3 , 4 ], playing important roles in arginine/agmatine metabolism, the urea cycle, histidine degradation, and other pathways.

Arginase, which catalyses the conversion of arginine to urea and ornithine, is one of the five members of the urea cycle enzymes that convert ammonia to urea as the principal product of nitrogen excretion [ 5 ]. There are several arginase isozymes that differ in catalytic, molecular and immunological properties. Deficiency in the liver isozyme leads to argininemia, which is usually associated with hyperammonemia.

Agmatinase hydrolyses agmatine to putrescine, the precursor for the biosynthesis of higher polyamines, spermidine and spermine. In addition, agmatine may play an important regulatory role in mammals.

Formiminoglutamase catalyses the fourth step in histidine degradation, acting to hydrolyse N-formimidoyl-L-glutamate to L-glutamate and formamide.

Proclavaminate amidinohydrolase is involved in clavulanic acid biosynthesis. Clavulanic acid acts as an inhibitor of a wide range of beta-lactamase enzymes that are used by various microorganisms to resist beta-lactam antibiotics. As a result, this enzyme improves the effectiveness of beta-lactamase antibiotics [ 6 ].

1. Crystal structure of agmatinase reveals structural conservation and inhibition mechanism of the ureohydrolase superfamily. J. Biol. Chem. 279, 50505-13
2. Crystal structure of human arginase I at 1.29-A resolution and exploration of inhibition in the immune response. Proc. Natl. Acad. Sci. U.S.A. 102, 13058-63
3. Oligomeric structure of proclavaminic acid amidino hydrolase: evolution of a hydrolytic enzyme in clavulanic acid biosynthesis. Biochem. J. 366, 423-34
4. Evolution of the arginase fold and functional diversity. Cell. Mol. Life Sci. 65, 2039-55
5. Developmental and hormonal regulation of the Xenopus liver-type arginase gene. Eur. J. Biochem. 211, 891-8