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Literature summary for 2.3.1.37 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
Search for more literature for 2.3.1.37

Cloned(Commentary)

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

Protein Variants

Protein Variants Comment Organism
F557X site-directed mutagenesis, a ALAS2 exon 11, c.1670-1671TC>GA mutation Homo sapiens
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
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]

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

Molecular Weight [Da]

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

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
succinyl-CoA + glycine Homo sapiens
-
 5-aminolevulinate + CoA + CO2
-
 r

Organism

Organism UniProt Comment Textmining
Homo sapiens P22557 gene alas2
-

Purification (Commentary)

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

Substrates and Products (Substrate)

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

Subunits

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

Synonyms

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

Temperature Optimum [°C]

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

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
additional information
-
 comparison of thermostability of wild-type and mutant ALAS2 aApoenzymes, overview Homo sapiens
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

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

Cofactor

Cofactor Comment Organism Structure
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

General Information Comment Organism
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