Pathways & interactions
Fumarylacetoacetase-like, C-terminal domain superfamily (IPR036663)
Short name: Fumarylacetoacetase_C_sf
- Fumarylacetoacetase (IPR005959)
- Uncharacterised conserved protein GguC (IPR009645)
- Fumarylacetoacetase-like, C-terminal (IPR011234)
- 4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase, C-terminal subunit (IPR012684)
- 4-hydroxyphenylacetate degradation bifunctional isomerase/decarboxylase, N-terminal subunit (IPR012686)
- 2-oxo-hepta-4-ene-1,7-dioic acid hydratase (IPR012690)
- 4-oxalocrotonate decarboxylase (IPR017630)
- 2-oxopent-4-enoate hydratase (IPR017632)
- 2-keto-4-pentenoate hydratase (IPR023793)
Fumarylacetoacetase (EC:126.96.36.199; 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 [PMID: 11154690]. 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 [PMID: 9101289, PMID: 16602095]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole [PMID: 10508789]. 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 [PMID: 10508789].
This superfamily represents the C-terminal domain of fumarylacetoacetase, as well as other domains that share a homologous alpha/beta structure, including:
- 5-carboxymethyl-2-hydroxymuconate delta-isomerase (CHM isomerase; EC:188.8.131.52), which catalyses the conversion of 5-carboxymethyl-2-hydroxymuconate to 5-carboxy-2-oxohept-3-enedioate [PMID: 2194841].
- 5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (OPET decarboxylase; EC:184.108.40.206), which catalyses the conversion of 5-oxopent-3-ene-1,2,5-tricarboxylate to 2-oxohept-3-enedioate and carbon dioxide.
- Bifunctional enzyme HpcE (OPET decarboxylase EC:220.127.116.11/HHDD isomerase EC:18.104.22.168), which is a duplication consisting of a tandem repeat of two FAH C-terminal-like domains. This enzyme is responsible for the degradation of 4-hydroxyphenylacetate, a product of tyrosine and phenylalanine metabolism also released by lignin catabolism [PMID: 11863436].
- 2-keto-4-pentenoate hydratase MhpD (EC:22.214.171.124; also known as 2-oxopent-4-enoate hydratase), which converts 4-hydroxy-2-oxopentanoate to 2-oxopent-4-enoate [PMID: 10537203].
- 4-oxalocrotonate decarboxylase (4-OD; EC:126.96.36.199), which catalyses the conversion of 4-oxalocrotonate to 2-oxopent-4-enoate and carbon dioxide [PMID: 10651637].
- 2-oxo-hepta-3-ene-1,7-dioic acid hydratase, which hydrates the double bond of 2-oxo-hepta-3-ene-1,7-dioic acid to form 4-hydroxy-2-oxo-heptane-1,7-dioic acid in the catabolism of 4-hydroxyphenylacetic acid.