Binding Site

Ureohydrolase, manganese-binding site (IPR020855)

Short name: Ureohydrolase_Mn_BS


The ureohydrolase superfamily includes arginase (EC:, agmatinase (EC:, formiminoglutamase (EC: and proclavaminate amidinohydrolase (EC: [PMID: 15355972]. These enzymes share a 3-layer alpha-beta-alpha structure [PMID: 15355972, PMID: 16141327, PMID: 12020346], and play 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 [PMID: 7916684]. 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 [PMID: 12020346].

Three conserved regions that contain charged residues which are involved in the binding of the two manganese ions in the active site are located in loop segments of the central beta-sheet [PMID: 8849731, PMID: 12020346, PMID: 15355972, PMID: 18360740]. The signature pattern of this entry contains two aspartate residues that are involved in manganese binding.

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0016813 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amidines
GO:0046872 metal ion binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns