InterPro domain: IPR013108

Amidohydrolases are a diverse superfamily of enzymes which catalyse the hydrolysis of amide or amine bonds in a large number of different substrates including urea, cytosine, AMP, formylmethanofuran, etc [ 1 , 2 ]. Also included in this superfamily are the phopshotriesterase enzymes, which hydrolyse P-O bonds. Members participate in a large number of processes including nucleotide metabolism, detoxification and neuronal development. They use a variety of divalent metal cofactors for catalysis: for example adenosine deaminase binds a single zinc ion, phopsphotriesterase binds two, while urease binds nickel. It has been postulated that since some of these proteins, such as those some of those involved in neuronal devlopment, appear to have lost their metal-binding centres, their function may simply be to bind, but not hydrolyse, their target molecules.

This entry represents a subset of amidohydrolase domains that participate in different functions including cytosine degradation, atrazine degradation and other metabolic processes. The structure of the domain from Escherichia coli has been studied, and like other amidohydrolases it forms a classical alpha-beta TIM-barrel fold [ 3 ]. The active site is located in the mouth of the enzyme barrel and contains a bound iron ion that coordinates a hydroxyl nucleophile. Substrate binding involves a significant conformational change that sequesters the reaction complex from solvent.

1. An evolutionary treasure: unification of a broad set of amidohydrolases related to urease. Proteins 28, 72-82
2. Divergent evolution of enzymatic function: mechanistically diverse superfamilies and functionally distinct suprafamilies. Annu. Rev. Biochem. 70, 209-46
3. The structure of Escherichia coli cytosine deaminase. J. Mol. Biol. 315, 687-97