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Information on EC 3.7.1.2 - fumarylacetoacetase and Organism(s) Mus musculus and UniProt Accession P35505

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EC Tree
     3 Hydrolases
         3.7 Acting on carbon-carbon bonds
             3.7.1 In ketonic substances
                3.7.1.2 fumarylacetoacetase
IUBMB Comments
Also acts on other 3,5- and 2,4-dioxo acids.
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This record set is specific for:
Mus musculus
UNIPROT: P35505
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
faa, fumarylacetoacetate hydrolase, fumarylacetoacetase, sscd1, eafah, atfah, faa hydrolase, acylpyruvase, ttha0809, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
FAA hydrolase
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fumarylacetoacetase
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fumarylacetoacetate hydrolase
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4-fumarylacetoacetate fumarylhydrolase
-
-
-
-
acylpyruvase
-
-
-
-
beta-diketonase
diketo acid hydrolase
-
-
-
-
FAA
-
-
-
-
fumarylacetoacetate hydrolase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
4-fumarylacetoacetate + H2O = acetoacetate + fumarate
show the reaction diagram
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
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of C-C bond
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C-C-bond cleavage
-
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hydrolysis of C-C bond
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-
-
-
SYSTEMATIC NAME
IUBMB Comments
4-fumarylacetoacetate fumarylhydrolase
Also acts on other 3,5- and 2,4-dioxo acids.
CAS REGISTRY NUMBER
COMMENTARY hide
9032-59-1
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4-fumarylacetoacetate + H2O
acetoacetate + fumarate
show the reaction diagram
-
-
-
?
4-fumarylacetoacetate + H2O
acetoacetate + fumarate
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4-fumarylacetoacetate + H2O
acetoacetate + fumarate
show the reaction diagram
-
-
-
?
4-fumarylacetoacetate + H2O
acetoacetate + fumarate
show the reaction diagram
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
metal ligand binding distance analysis from crystal structure
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3-[(3-carboxy-2-oxopropyl)hydroxyphosphinyl]acrylate
COPHPAA
4-[(2-carboxyethyl)-hydroxyphosphinyl]-3-oxobutyrate
CEHPOBA
4-(hydroxymethylphosphinoyl)-3-oxo-butanoic acid
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i.e. HMPOBA, competitive
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.0575
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kidney
0.0803
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liver
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
activity assay
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary cell
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
FAAA_MOUSE
419
0
46176
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
46000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
a high-resolution crystal structure of the FAH-CEHPOBA complex is soved at 1.35 A
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
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A134D
-
-
C193R
-
mutant may affect the active-site geometry
D233V
-
mutant
G158D
G207D
-
mutant may affect the active-site geometry
G369V
-
mutant may affect the active-site geometry
N16I
-
mutant may disrupt activity by causing misfolding
P249T
-
mutant may affect the active-site geometry
P261L
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mutant may cause general structural effects or misfolding by disrupting the hydrophobic core, the native mainchain conformation and/or important electrostatic interactions
P342L
-
mutant may cause general structural effects or misfolding by disrupting the hydrophobic core, the native mainchain conformation and/or important electrostatic interactions
S405H
-
mutant may cause general structural effects or misfolding by disrupting the hydrophobic core, the native mainchain conformation and/or important electrostatic interactions
V166G
-
mutant may affect the active-site geometry
W234G
-
mutant may affect the active-site geometry
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme, fusion protein is cleaved from the fusion tag by bovine thrombin
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
for expression in Escherichia coli
generation of a Fah-knockout mutant as a model of hereditary tyrosinemia type I. Transplantation of wild-type bone marrow cells from fully allogeneic BALB/c donors into Fah-knockout mutant after lethal total body irradiation results in healthy recipients without pharmacological support
expression as glutathione S-transferase fusion protein
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proteome analysis. FAH protein level is down-regulated in the Fe2+ adequate fed TNF-deltaARE mutant and up-regulated in the Fe2+ low fed TNF-deltaARE mutant compared to wild-type
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
hereditary tyrosinaemia type 1 results from deficiency of fumarylacetoacetase
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Meister, A.; Greenstein, J.P.
Enzymatic hydrolysis of 2,4-diketo acids
J. Biol. Chem.
175
573-588
1948
Oryctolagus cuniculus, Felis catus, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Klebig, M.L.; Russell, L.B.; Rinchik, E.M.
Murine fumarylacetoacetate hydrolase (Fah) gene is disrupted by a neonatally lethal albino deletion that defines the hepatocyte-specific developmental regulation 1 (hsdr-1) locus
Proc. Natl. Acad. Sci. USA
89
1363-1367
1992
Mus musculus
Manually annotated by BRENDA team
Grompe, M.; Al-Dhalimy, M.; Finegold, M.; Ou, C.N.; Burlingame, T.; Kennaway, N.G.; Soriano, P.
Loss of fumarylacetoacetate hydrolysis is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice
Genes Dev.
7
2298-2307
1993
Mus musculus
Manually annotated by BRENDA team
Timm, D.E.; Mueller, H.A.; Bhanumoorthy, P.; Harp, J.M.; Bunick, G.J.
Crystal structure and mechanism of a carbon-carbon bond hydrolase
Structure
7
1023-1033
1999
Mus musculus
Manually annotated by BRENDA team
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
J. Biol. Chem.
276
15284-15291
2001
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Grogan, G.
Emergent mechanistic diversity of enzyme-catalysed beta-diketone cleavage
Biochem. J.
388
721-730
2005
Bos taurus, Mus musculus
Manually annotated by BRENDA team
Bateman, R.L.; Ashworth, J.; Witte, J.F.; Baker, L.J.; Bhanumoorthy, P.; Timm, D.E.; Hurley, T.D.; Grompe, M.; McClard, R.W.
Slow-onset inhibition of fumarylacetoacetate hydrolase by phosphinate mimics of the tetrahedral intermediate: kinetics, crystal structure and pharmacokinetics
Biochem. J.
402
251-260
2007
Homo sapiens, Mus musculus (P35505), Mus musculus
Manually annotated by BRENDA team
Eggenhofer, E.; Popp, F.C.; Renner, P.; Slowik, P.; Neuwinger, A.; Piso, P.; Geissler, E.K.; Schlitt, H.J.; Dahlke, M.H.
Allogeneic bone marrow transplantation restores liver function in Fah-knockout mice
Exp. Hematol.
36
1507-1513
2008
Mus musculus (P35505)
Manually annotated by BRENDA team
Werner, T.V.; Hoermannsperger, G.; Schuemann, K.; Hoelzlwimmer, G.; Tsuji, S.; Haller, D.
Intestinal epithelial cell proteome from wild type and TNFARE/WT mice: effect of iron on the development of chronic ileitis
J. Proteome Res.
8
3252-3264
2009
Mus musculus
Manually annotated by BRENDA team