InterPro domain: IPR005959

Fumarylacetoacetase ( 3.7.1.2 ; also known as fumarylacetoacetate hydrolase or FAH) catalyses the hydrolytic cleavage of a carbon-carbon bond in fumarylacetoacetate to yield fumarate and acetoacetate as the final step in phenylalanine and tyrosine degradation [ 1 ]. This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinaemia, which is associated with liver and kidney abnormalities and neurological disorders [ 2 , 3 ]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole [ 4 ]. FAH folds into two domains: an N-terminal domain SH3-like beta-barrel, and a C-terminal with an unusual fold consisting of three layers of beta-sheet structures [ 5 ].

1. Mechanistic inferences from the crystal structure of fumarylacetoacetate hydrolase with a bound phosphorus-based inhibitor. J. Biol. Chem. 276, 15284-91
2. The genetic tyrosinemias. null 142C, 121-6
3. Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview. Hum. Mutat. 9, 291-9
4. Crystal structure and mechanism of a carbon-carbon bond hydrolase. Structure 7, 1023-33