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Literature summary for 4.2.1.75 extracted from

  • Mathews, M.A.; Schubert, H.L.; Whitby, F.G.; Alexander, K.J.; Schadick, K.; Bergonia, H.A.; Phillips, J.D.; Hill, C.P.
    Crystal structure of human uroporphyrinogen III synthase (2001), EMBO J., 20, 5832-5839.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
expression of the N-terminal His-tagged wild-type and mutant enzymes in Escherichia coli BL21(DE3) Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
5 mg/ml purified recombinant wild-type and selenomethionine-enzyme, sitting drop vapour diffusion method, 4°C, equal volumes of protein solution, containing 10 mM Tris-HCl, pH 7.5, 1 mM dithiothreitol, and reservoir solution, containing 20% 2-methyl-2,4-pentanediol, 100 mM MES, pH 6.0, X-ray diffraction structure determination and analysis at 1.85-2.1 A resolution Homo sapiens

Protein Variants

Protein Variants Comment Organism
A66V clinical mutation, altered tertiary structure Homo sapiens
E127A site-directed mutagenesis, unaltered activity level compared to the wild-type enzyme Homo sapiens
E249stop clinical mutation, truncated protein, loss of helix 12 Homo sapiens
G225S clinical mutation, altered tertiary structure Homo sapiens
I129T clinical mutation, altered tertiary structure Homo sapiens
K220A site-directed mutagenesis, slightly increased activity compared to the wild-type enzyme Homo sapiens
L4F clinical mutation, altered tertiary structure Homo sapiens
additional information the naturally occuring clinical mutations lead to loss in activity due to structural alterations in the enzymes, overview Homo sapiens
P248Q clinical mutation, altered tertiary structure Homo sapiens
P53L clinical mutation, altered tertiary structure Homo sapiens
R65A site-directed mutagenesis, slightly reduced activity compared to the wild-type enzyme Homo sapiens
S197A site-directed mutagenesis, unaltered activity level compared to the wild-type enzyme Homo sapiens
S212P clinical mutation, altered tertiary structure Homo sapiens
S63A site-directed mutagenesis, unaltered activity level compared to the wild-type enzyme Homo sapiens
T103A site-directed mutagenesis, reduced activity compared to the wild-type enzyme Homo sapiens
T227A site-directed mutagenesis, slightly increased activity compared to the wild-type enzyme Homo sapiens
T228A site-directed mutagenesis, conserved residue near to the active site cleft, reduced activity compared to the wild-type enzyme Homo sapiens
T228M clinical mutation, altered tertiary structure Homo sapiens
T62A site-directed mutagenesis, conserved residue near to the active site cleft, unaltered activity level compared to the wild-type enzyme Homo sapiens
V3F clinical mutation, altered tertiary structure Homo sapiens
Y168A site-directed mutagenesis, reduced activity compared to the wild-type enzyme Homo sapiens
Y19C clinical mutation, altered tertiary structure Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
hydroxymethylbilane Homo sapiens linear tetrapyrrole, fourth step in the biosynthesis of porphyrin, essential reaction, decreased enzyme activity leads to the autosomal recessive disorder congenital erythropetic porphyria uroporphyrinogen-III + H2O macrocyclic uroporphyrinogen III is a precurosr for synthesis of diverse compounds, e.g. heme, siroheme, chlorophyll, F430, and vitamin B12 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens P10746
-
-

Reaction

Reaction Comment Organism Reaction ID
hydroxymethylbilane = uroporphyrinogen III + H2O in the presence of hydroxymethylbilane synthase EC 4.3.1.8, enzyme forms uroporphyrinogen III from porphobilinogen, reaction mechanism, does not require acid/base catalysis, active site structure Homo sapiens

Renatured (Commentary)

Renatured (Comment) Organism
recombinant His-tagged wild-type enzyme from Escherichia coli, to homogeneity Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
hydroxymethylbilane
-
Homo sapiens uroporphyrinogen-III + H2O
-
?
hydroxymethylbilane linear tetrapyrrole, fourth step in the biosynthesis of porphyrin, essential reaction, decreased enzyme activity leads to the autosomal recessive disorder congenital erythropetic porphyria Homo sapiens uroporphyrinogen-III + H2O macrocyclic uroporphyrinogen III is a precurosr for synthesis of diverse compounds, e.g. heme, siroheme, chlorophyll, F430, and vitamin B12 ?

Subunits

Subunits Comment Organism
More observed interdomain flexibility might be important for catalysis, the active site is located between the domains Homo sapiens

Synonyms

Synonyms Comment Organism
U3S
-
Homo sapiens
Uroporphyrinogen III synthase
-
Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.2
-
assay at Homo sapiens