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Literature summary for 3.7.1.2 extracted from

  • Bateman, R.L.; Bhanumoorthy, P.; Witte, J.F.; McClard, R.W.; Grompe, M.; Timm, D.E.
    Mechanistic inferences from the crystal structure of fumarylacetoacetate hydrolase with a bound phosphorus-based inhibitor (2001), J. Biol. Chem., 276, 15284-15291.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
expression as glutathione S-transferase fusion protein Mus musculus
expression of C-terminally His-tagged enzyme in a bacterial expression system Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
inhibitor complexed enzyme, 3 mg/ml purified hanging drop vapor diffusion method, room temperature, in a 2:1 ratio with precipitant solution, containing 17-18% PEG 8000, 0.03-0.15 nickel acetate, no to 0.24 M sodium acetate, 0.1 M sodium cacodylate, pH 6.5, soaking in inhibitor 4-(hydroxymethylphosphinoyl)-3-oxo-butanoic acid solution for 16 h prior to data collection via X-ray diffraction, structure determination and analysis at 1.3 A resolution Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
4-(hydroxymethylphosphinoyl)-3-oxo-butanoic acid i.e. HMPOBA, competitive Homo sapiens
4-(hydroxymethylphosphinoyl)-3-oxo-butanoic acid i.e. HMPOBA, competitive Mus musculus

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+
-
Homo sapiens
Ca2+ bound to the free enzyme Mus musculus
Mg2+ bound to the active site of the enzyme Mus musculus
Mg2+ bound to the active site of the enzyme Homo sapiens
additional information metal ligand binding distance analysis from crystal structure Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4-fumarylacetoacetate + H2O Mus musculus final step of Phe and Tyr degradation, essential metabolic function, loss of enzyme function causes the fatal metabolic disease hereditary tyrosinemia type I, i.e. HT1 acetoacetate + fumarate
-
?
4-fumarylacetoacetate + H2O Homo sapiens final step of Phe and Tyr degradation, essential metabolic function, loss of enzyme function causes the fatal metabolic disease hereditary tyrosinemia type I, i.e. HT1 acetoacetate + fumarate
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme Homo sapiens
recombinant His-tagged enzyme, fusion protein is cleaved from the fusion tag by bovine thrombin Mus musculus

Reaction

Reaction Comment Organism Reaction ID
4-fumarylacetoacetate + H2O = acetoacetate + fumarate also acts on other 3,5- and 2,4-dioxo acids, mechanism involves a catalytic metal ion, a Glu/His catalyic diad, and a charged oxyanion hole Homo sapiens
4-fumarylacetoacetate + H2O = acetoacetate + fumarate also acts on other 3,5- and 2,4-dioxo acids, mechanism involves a catalytic metal ion, a Glu/His catalyic diad, and a charged oxyanion hole, side chain mobility in the active site Mus musculus

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4-fumarylacetoacetate + H2O
-
Homo sapiens acetoacetate + fumarate
-
?
4-fumarylacetoacetate + H2O final step of Phe and Tyr degradation, essential metabolic function, loss of enzyme function causes the fatal metabolic disease hereditary tyrosinemia type I, i.e. HT1 Mus musculus acetoacetate + fumarate
-
?
4-fumarylacetoacetate + H2O final step of Phe and Tyr degradation, essential metabolic function, loss of enzyme function causes the fatal metabolic disease hereditary tyrosinemia type I, i.e. HT1 Homo sapiens acetoacetate + fumarate
-
?
4-fumarylacetoacetate + H2O formation of a tetrahedral alkoxy transition state intermediate Mus musculus acetoacetate + fumarate
-
?

Synonyms

Synonyms Comment Organism
beta-diketonase
-
Mus musculus
beta-diketonase
-
Homo sapiens
FAH
-
Mus musculus
FAH
-
Homo sapiens
fumarylacetoacetate hydrolase
-
Mus musculus
fumarylacetoacetate hydrolase
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Mus musculus
37
-
assay at Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.085
-
4-(hydroxymethylphosphinoyl)-3-oxo-butanoic acid 37°C, recombinant enzyme Homo sapiens