Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary 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)

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

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
4.2.1.75 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

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

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
4.2.1.75 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

EC Number Organism UniProt Comment Textmining
4.2.1.75 Homo sapiens P10746
-
-

Reaction

EC Number Reaction Comment Organism Reaction ID
4.2.1.75 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
a

Renatured (Commentary)

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

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4.2.1.75 hydroxymethylbilane
-
 Homo sapiens uroporphyrinogen-III + H2O
-
 ?
4.2.1.75 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

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

Synonyms

EC Number Synonyms Comment Organism
4.2.1.75 U3S
-
 Homo sapiens
4.2.1.75 Uroporphyrinogen III synthase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
4.2.1.75 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
4.2.1.75 8.2
-
 assay at Homo sapiens