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.
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 |