PTHR43069

FUMARYLACETOACETASE

PANTHER entry
Member databasePANTHER
PANTHER typefamily

Description
Imported from 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, 5]
. 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
[2, 4]
. The enzyme mechanism involves a catalytic metal ion, a Glu/His catalytic dyad, and a charged oxyanion hole
[3]
. 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
[3]
.

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
[7, 6]
.

References
Imported from IPR005959

1.Mechanistic inferences from the crystal structure of fumarylacetoacetate hydrolase with a bound phosphorus-based inhibitor. Bateman RL, Bhanumoorthy P, Witte JF, McClard RW, Grompe M, Timm DE. J. Biol. Chem. 276, 15284-91, (2001). View articlePMID: 11154690

2.The genetic tyrosinemias. Scott CR. 142C, 121-6, (2006). View articlePMID: 16602095

3.Crystal structure and mechanism of a carbon-carbon bond hydrolase. Timm DE, Mueller HA, Bhanumoorthy P, Harp JM, Bunick GJ. Structure 7, 1023-33, (1999). View articlePMID: 10508789

4.Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview. St-Louis M, Tanguay RM. Hum. Mutat. 9, 291-9, (1997). View articlePMID: 9101289

5.Sugar suppresses cell death caused by disruption of fumarylacetoacetate hydrolase in Arabidopsis. Zhi T, Zhou Z, Huang Y, Han C, Liu Y, Zhu Q, Ren C. Planta 244, 557-71, (2016). PMID: 27097641

6.Pyomelanin formation in Aspergillus fumigatus requires HmgX and the transcriptional activator HmgR but is dispensable for virulence. Keller S, Macheleidt J, Scherlach K, Schmaler-Ripcke J, Jacobsen ID, Heinekamp T, Brakhage AA. PLoS One 6, e26604, (2011). PMID: 22046314

7.Production of pyomelanin, a second type of melanin, via the tyrosine degradation pathway in Aspergillus fumigatus. Schmaler-Ripcke J, Sugareva V, Gebhardt P, Winkler R, Kniemeyer O, Heinekamp T, Brakhage AA. Appl Environ Microbiol 75, 493-503, (2009). PMID: 19028908

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