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Literature summary extracted from

  • Bishop, D.F.; Tchaikovskii, V.; Nazarenko, I.; Desnick, R.J.
    Molecular expression and characterization of erythroid-specific 5-aminolevulinate synthase gain-of-function mutations causing X-linked protoporphyria (2013), Mol. Med., 19, 18-25.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.37 recombinant expression of MBP-fusion wild-type and mutant enzymes Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.3.1.37 F557X site-directed mutagenesis, a ALAS2 exon 11, c.1670-1671TC>GA mutation Homo sapiens
2.3.1.37 additional information generation of two deletion mutants DELTAAT and DELTAAGTG enzymes. Compared to the purified wild-type enzyme, the deletion mutants show 1.8 and 3.1fold increased activity,respectively, compared to the wild-type enzyme Homo sapiens
2.3.1.37 Q548X naturally occuring mutation involved in X-linked protoporphyria, 1.6fold increased activity compared to the wild-type enzyme. The increased activity Q548X enzyme does not bind to succinyl-CoA synthetase Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.37 0.0357
-
 succinyl-CoA pH 7.4, 37°C, recombinant mutant DELTAAGTG Homo sapiens
2.3.1.37 0.0398
-
 succinyl-CoA pH 7.4, 37°C, recombinant mutant DELTAAT Homo sapiens
2.3.1.37 0.0401
-
 succinyl-CoA pH 7.4, 37°C, recombinant mutant DELTAG Homo sapiens
2.3.1.37 0.0407
-
 succinyl-CoA pH 7.4, 37°C, recombinant wild-type enzyme Homo sapiens
2.3.1.37 7.5
-
 glycine pH 7.4, 37°C, recombinant mutant DELTAAGTG Homo sapiens
2.3.1.37 7.7
-
 glycine pH 7.4, 37°C, recombinant mutant F557X Homo sapiens
2.3.1.37 9.3
-
 glycine pH 7.4, 37°C, recombinant wild-type enzyme Homo sapiens
2.3.1.37 12
-
 glycine pH 7.4, 37°C, recombinant mutant Q548X Homo sapiens
2.3.1.37 13
-
 glycine pH 7.4, 37°C, recombinant mutant DELTAAT Homo sapiens
2.3.1.37 13.5
-
 glycine pH 7.4, 37°C, recombinant mutant DELTAG Homo sapiens
2.3.1.37 36.3
-
 succinyl-CoA pH 7.4, 37°C, recombinant mutant F557X Homo sapiens
2.3.1.37 52.4
-
 succinyl-CoA pH 7.4, 37°C, recombinant mutant Q548X Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.3.1.37 52000
-
 x * 54000, recombinant wild-type enzyme, SDS-PAGE, x * 52000, recombinant mutant F557X, SDS-PAGE Homo sapiens
2.3.1.37 54000
-
 x * 54000, recombinant wild-type enzyme, SDS-PAGE, x * 52000, recombinant mutant F557X, SDS-PAGE Homo sapiens

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 Homo sapiens
-
 5-aminolevulinate + CoA + CO2
-
 r

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.37 Homo sapiens P22557 gene alas2
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.37 recombinant MBP-fusion wild-type and mutant enzymes 29-114fold by amylose affinity chromatography and gel filtration Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.37 succinyl-CoA + glycine
-
 Homo sapiens 5-aminolevulinate + CoA + CO2
-
 r

Subunits

EC Number Subunits Comment Organism
2.3.1.37 ? x * 54000, recombinant wild-type enzyme, SDS-PAGE, x * 52000, recombinant mutant F557X, SDS-PAGE Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.3.1.37 ALAS2
-
 Homo sapiens
2.3.1.37 erythroid-specific 5-aminolevulinate synthase
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.3.1.37 37
-
 assay at Homo sapiens

Temperature Stability [°C]

EC Number Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
2.3.1.37 additional information
-
 comparison of thermostability of wild-type and mutant ALAS2 aApoenzymes, overview Homo sapiens
2.3.1.37 45
-
 t1/2 of the wild-type is 11.7 min, and t1/2 of mutant enzymes are between 3.8 and 12.8 min Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.37 7.4
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
2.3.1.37 pyridoxal 5'-phosphate dependent on, wild-type Km is 0.0000215 nM, Km values of mutant enzymes are between 0.0000062 nM and 0.00065 nM Homo sapiens

General Information

EC Number General Information Comment Organism
2.3.1.37 malfunction X-linked protoporphyria is a erythropoietic porphyria due to gain-of-function mutations in the erythroid-specific aminolevulinate synthase gene (ALAS2). Two exon 11 small deletions, c.1699_1670DELTAAT and c.1706_1709DELTAAGTG (DELTAAGTG), that prematurely truncate or elongate the ALAS2 polypeptide, are reported to increase enzymatic activity 20 to 40fold, causing the erythroid accumulation of protoporphyrins, cutaneous photosensitivity and liver disease Homo sapiens