Literature summary for 4.2.1.75 extracted from

Fortian, A.; Castano, D.; Gonzalez, E.; Lain, A.; Falcon-Perez, J.M.; Millet, O.
Structural, thermodynamic, and mechanistical studies in uroporphyrinogen III synthase: Molecular basis of congenital erythropoietic porphyria (2011), Adv. Protein Chem. Struct. Biol., 83, 43-74.

Cloned(Commentary)

Cloned (Comment)	Organism
expression of wild-type UROIIIS and 25 point mutants in Escherichia coli	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
A104V	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
A66V	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
A69T	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
C73R	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria, the mutant protein retains partial catalytic activity but shows reduced the enzyme stability	Homo sapiens
E81D	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
G188R	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
G188W	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
G225S	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
G236V	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
H173Y	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
I129T	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
I219S	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
L237P	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
L4F	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
additional information	genotype/phenotype analysis of the studied cases of congenital erythropoietic porphyria, overview	Homo sapiens
P248Q	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
P53L	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
Q187P	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
S212P	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
S47P	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
T228M	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
T62A	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
V3F	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
V82F	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
V99A	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens
Y19C	a naturally occuring mutation in the enzyme involved in congenital erythropoietic porphyria	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
additional information	-	additional information	kinetic and thermodynamic analysis, thermodynamic versus kinetic stability, overview	Homo sapiens
0.00015	-	Hydroxymethylbilane	pH not specified in the publication, temperature not specified in the publication	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cytosol	-	Homo sapiens	5829	-

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
28000	-	x * 28000	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
hydroxymethylbilane	Homo sapiens	-	uroporphyrinogen III + H2O	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-
Pseudomonas syringae	Q88B90	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
additional information	UROIIIS is processed via the proteosome pathway, which can be reverted by reversibly inhibiting the proteosome with the aldehyde MG132	Homo sapiens

Purification (Commentary)

Purification (Comment)	Organism
recombinant wild-type UROIIIS and 25 point mutants in Escherichia coli to over 97% purity	Homo sapiens

Reaction

Reaction	Comment	Organism	Reaction ID
hydroxymethylbilane = uroporphyrinogen III + H2O	reaction mechanism, modeling involving Tyr168, overview	Homo sapiens	a

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
33.37	-	pH not specified in the publication, temperature not specified in the publication	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
hydroxymethylbilane	-	Homo sapiens	uroporphyrinogen III + H2O	-	?
hydroxymethylbilane	enzymatic conversion of preuroporphyrinogen. The substrate must bind the enzyme in a conformation that prevents C19 from reacting with C20	Homo sapiens	uroporphyrinogen III + H2O	-	?

Subunits

Subunits	Comment	Organism
?	x * 28000	Homo sapiens
More	three-dimensional structure, overview	Homo sapiens
More	three-dimensional structure, overview	Pseudomonas syringae

Synonyms

Synonyms	Comment	Organism
UROIIIS	-	Homo sapiens
UROIIIS	-	Pseudomonas syringae
Uroporphyrinogen III synthase	-	Homo sapiens
Uroporphyrinogen III synthase	-	Pseudomonas syringae

Temperature Stability [°C]

Temperature Stability Minimum [°C]	Temperature Stability Maximum [°C]	Comment	Organism
additional information	-	the enzyme is metathermostabile, irreversible denaturation process. At physiological temperature and in vitro, UROIIIS has a half-life time of 61.1 h, a long time for the enzyme to exert its function in the cell, dynamic behavior of the protein, three-state model, overview. Thermodynamic versus kinetic stability, overview	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	congenital erythropoietic porphyria is a rare autosomal disease ultimately related to deleterious mutations in uroporphyrinogen III synthase. In absence or dysfunction of the enzyme, hydroxymethylbilane spontaneously degrades to the by-product uroporphyrinogen I, which cannot lead to the heme group and accumulates in the body, producing some of the symptoms observed in congenital erythropoietic porphyria patients, phenotype, structural and molecular basis, overview	Homo sapiens
physiological function	UROIIIS is the fourth enzyme of the biosynthetic route of the heme group and catalyzes the cyclization of the linear tetrapyrrol hydroxymethylbilane, inverting the configuration in one of the aromatic rings. It accelerates the production of uroporphyrinogen III (an energetically unfavorable chemical reaction) at the same time as it suppresses the spontaneous reaction pathway to yield uroporphyrinogen I	Homo sapiens