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Literature summary for 3.5.1.6 extracted from

  • Van Kuilenburg, A.; Dobritzsch, D.; Meijer, J.; Krumpel, M.; Selim, L.; Rashed, M.; Assmann, B.; Meinsma, R.; Lohkamp, B.; Ito, T.; Abeling, N.; Saito, K.; Eto, K.; Smitka, M.; Engvall, M.; Zhang, C.; Xu, W.; Zoetekouw, L.; Hennekam, R.
    beta-Ureidopropionase deficiency: phenotype, genotype and protein structural consequences in 16 patients (2012), Biochim. Biophys. Acta, 1822, 1096-1108.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
gene UPB1, located on chromosome 22q11.2, DNA and amino acid sequence determination and analysis, sequence comparisons and genomic organization analysis, genotyping of beta-ureidopropionase deficient patients as well as the analysis of the mutations in a three-dimensional framework, PCR enzyme expression analysis, overview. Recombinant heterologous expression of wild-type and mutant enzymes in Escherichia coli strain C41(DE3)pRARE2, all mutations yield mutant beta-ureidopropionase proteins with significantly decreased activity Homo sapiens

Protein Variants

Protein Variants Comment Organism
G235R naturally occuring mutation and site-directed mutagenesis, inactive mutant. Mutation G235R introduces a large amino acid side chain for which there is no space available at this location. The larger structural rearrangements in the active site cavity required to prevent clashes with surrounding residues are expected to lead to enzyme inactivity and misfolding and defects in oligomerization, inability to obtain significant expression of soluble protein for this mutant Homo sapiens
L13S naturally occuring mutation and site-directed mutagenesis, the mutation results in folding defects and oligomer assembly impairment, the mutant shows reduced activity compared to the wild-type enzyme Homo sapiens
R236W naturally occuring mutation and site-directed mutagenesis, the mutant shows highly reduced activity compared to the wild-type enzyme Homo sapiens
R326Q naturally occuring mutation and site-directed mutagenesis, the mutation results in folding defects and oligomer assembly impairment, inactive mutant Homo sapiens
S264R naturally occuring mutation and site-directed mutagenesis,mutation S264R abolishes the hydrogen bond to Y314, which may be important for structural fixation of a residue stretch that is involved in shaping the entrance to the active site, the mutant shows reduced activity compared to the wild-type enzyme Homo sapiens
T359M naturally occuring mutation and site-directed mutagenesis, the mutation results in folding defects and oligomer assembly impairment, the mutant shows highly reduced activity compared to the wild-type enzyme Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
43158
-
4 * 43158, sequence calculation, structure analysis by dynamic light scattering and circular dichroism spectroscopy, and modeling, overview Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3-ureidobutyrate + H2O Homo sapiens
-
2-methyl-beta-alanine + CO2 + NH3
-
?
3-ureidopropanoate + H2O Homo sapiens
-
beta-alanine + CO2 + NH3
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9UBR1 gene UPB1
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and mutant enzymes from Escherichia coli strain C41(DE3)pRARE2 by nickel affinity chromatography, desalting gel filtration, and cleavage of the tag by His-tagged 3C protease, followed by gel filtration and anion exchange chromatography Homo sapiens

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
0.0167
-
purified recombinant detagged mutant L13S, pH and temperature not specified in the publication Homo sapiens
0.0558
-
purified recombinant detagged mutant S264R, pH and temperature not specified in the publication Homo sapiens
0.282
-
purified recombinant detagged wild-type enzyme, pH and temperature not specified in the publication Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-ureidobutyrate + H2O
-
Homo sapiens 2-methyl-beta-alanine + CO2 + NH3
-
?
3-ureidopropanoate + H2O
-
Homo sapiens beta-alanine + CO2 + NH3
-
?

Subunits

Subunits Comment Organism
tetramer 4 * 43158, sequence calculation, structure analysis by dynamic light scattering and circular dichroism spectroscopy, and modeling, overview Homo sapiens

General Information

General Information Comment Organism
malfunction beta-ureidopropionase deficient patients show neurological abnormalities (intellectual disabilities, seizures, abnormal tonus regulation, microcephaly, and malformations on neuro-imaging) and markedly elevated levels of N-carbamyl-beta-alanine and N-carbamyl-beta-aminoisobutyric acid in urine and plasma, phenotypes of six missense and one splice-site mutants, overview Homo sapiens
metabolism beta-ureidopropionase is the third enzyme of the pyrimidine degradation pathway Homo sapiens
additional information the catalytically crucial cysteine C233 performs the nucleophilic attack on the substrate resulting in the covalent acyl-enzyme complex. Residue R236 is part of the active site and has a putative role in binding the carboxyl group of the substrate. Analysis of a homology model of human beta-ureidopropionase generated using the crystal structure of the enzyme from Drosophila melanogaster indicated that the point mutations p.G235R, p.R236W and p.S264R lead to amino acid exchanges in the active site and therefore affect substrate binding and catalysis Homo sapiens