Fumarylacetoacetase (; 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 []. 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 [, ]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: anN-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].This entry represents the N-terminal domain superfamily of fumarylacetoacetase. This domain adopts a structure consisting of an SH3-like barrel [].
Fumarylacetoacetase (; 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 [, ]. This is an essential metabolic function in humans, the lack of FAH causing type I tyrosinemia, which is associated with liver and kidney abnormalities and neurological disorders [, ]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].In Aspergillus fumigatus, this enzyme is part of the L-tyrosine degradation gene cluster that mediates the biosynthesis of the brownish pigment pyomelanin as an alternative melanin [, ].
Fumarylacetoacetase (; 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 []. 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 [, ]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].This entry represents the N-terminal domain of fumarylacetoacetase. This domain adopts a structure consisting of an SH3-like barrel [].
Fumarylacetoacetase (; 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 []. 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 [, ]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].This superfamily represents the C-terminal domain of fumarylacetoacetase, as well as other domains that share a homologous α/β structure, including:5-carboxymethyl-2-hydroxymuconate delta-isomerase (CHM isomerase; ), which catalyses the conversion of 5-carboxymethyl-2-hydroxymuconate to 5-carboxy-2-oxohept-3-enedioate [].5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (OPET decarboxylase; ),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 /HHDD isomerase ), 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 []. 2-keto-4-pentenoate hydratase MhpD (; also known as 2-oxopent-4-enoate hydratase), which converts 4-hydroxy-2-oxopentanoate to 2-oxopent-4-enoate [].4-oxalocrotonate decarboxylase (4-OD; ), which catalyses the conversion of 4-oxalocrotonate to 2-oxopent-4-enoate and carbon dioxide [].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.
Fumarylacetoacetase (; 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 []. 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 [, ]. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole []. FAH folds into two domains: an N-terminal domain SH3-like β-barrel, and a C-terminal with an unusual fold consisting of three layers of β-sheet structures [].This entry represents the C-terminal domain of fumarylacetoacetase, as well as other domains that share a homologous α/β structure, including:5-carboxymethyl-2-hydroxymuconate delta-isomerase (CHM isomerase; ), which catalyses the conversion of 5-carboxymethyl-2-hydroxymuconate to 5-carboxy-2-oxohept-3-enedioate [].5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (OPET decarboxylase; ), 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 /HHDD isomerase ), whichis 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 []. 2-keto-4-pentenoate hydratase MhpD (; also known as 2-oxopent-4-enoate hydratase), which converts 4-hydroxy-2-oxopentanoate to 2-oxopent-4-enoate [].4-oxalocrotonate decarboxylase (4-OD; ), which catalyses the conversion of 4-oxalocrotonate to 2-oxopent-4-enoate and carbon dioxide [].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.
