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Literature summary extracted from

  • Fratz, E.J.; Hunter, G.A.; Ferreira, G.C.
    Expression of murine 5-aminolevulinate synthase variants causes protoporphyrin IX accumulation and light-induced mammalian cell death (2014), PLoS ONE, 9, e93078.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.3.1.37 medicine delivery of stable and highly active ALAS2 variants has the potential to expand and improve upon current photodynamic therapies regimes Mus musculus

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.37 gene ALAS, recombinant expression in HeLa cells, stable expression of enzyme variants in K-562 cells Mus musculus

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.37 K313A site-directed mutagenesis, inactive mutant Mus musculus
2.3.1.37 additional information generation of enzyme mutant with mutated mitochondrial presequences, at residues C11 C38, and C70, and a mutation in the active site loop Expression of the mutants in human cells causes significant cellular accumulation of protoporphyrin IX, particularly in the membrane. ALAS2 expression results in an increase in cell death in comparison to aminolevulinic acid treatment producing a similar amount of protoporphyrin IX. Supplementation of cell culture medium with glycine leads to increased protoporphyrin IX accumulation in Malas2-expressing HeLa cells Mus musculus
2.3.1.37 R433K site-directed mutagenesis, mALAS2 variant with a mutated presequence, the mutation results in an increase in activity to twice that of the wild-type enzyme, i.e. a 2fold increase in the kcat value and a 1.65 to 1.85fold enhancement in the specificity constants for glycine and succinyl-CoA over those of wild-type, mature mALAS2, 2.5fold increase in protoporphyrin IX accumulation in HeLa cells expressing the R433K precursor with a mutated presequence Mus musculus
2.3.1.37 V423L/Y428R/P432E/R433I/G434N/E435Q/L437K site-directed mutagenesis, Mus musculus

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.37 heme feedback inhibition of mitochondrial import Mus musculus

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.1.37 mitochondrion
-
Mus musculus 5739
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.37 succinyl-CoA + glycine Mus musculus
-
5-aminolevulinate + CoA + CO2
-
?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.37 Mus musculus P08680 gene alas2
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.37 succinyl-CoA + glycine
-
Mus musculus 5-aminolevulinate + CoA + CO2
-
?

Synonyms

EC Number Synonyms Comment Organism
2.3.1.37 5-aminolevulinate synthase
-
Mus musculus
2.3.1.37 ALAS
-
Mus musculus

Expression

EC Number Organism Comment Expression
2.3.1.37 Mus musculus the enzyme is negatively regulated by heme at the level of mitochondrial import down

General Information

EC Number General Information Comment Organism
2.3.1.37 malfunction mutations of the murine ALAS2 active site loop result in increased production of protoporphyrin IX, the precursor for heme. Generation of protoporphyrin IX is a crucial component in the widely used photodynamic therapies of cancer and other dysplasias. ALAS2 variants that cause high levels of protoporphyrin IX accumulation provide a means of targeted, and potentially enhanced, photosensitization. ALAS2-induced protoporphyrin IX accumulation followed by light exposure combined with paclitaxel treatment causes cell death Mus musculus
2.3.1.37 metabolism 5-aminolevulinate synthase catalyzes the first committed step of heme biosynthesis in animals Mus musculus