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Literature summary for 2.3.1.37 extracted from

  • Stojanovski, B.M.; Ferreira, G.C.
    Murine erythroid 5-aminolevulinate synthase: adenosyl-binding site Lys221 modulates substrate binding and catalysis (2015), FEBS open bio, 5, 824-831.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.3.1.37

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of wild-type and mutant enzymes Mus musculus

Protein Variants

Protein Variants Comment Organism
K221V random mutagenesis, library screening, the mutation produces a 23fold increased Km for succinyl-CoA and a 97% decrease in kcat/Km for succinyl-CoA. This reduction in the specificity constant does not stem from lower affinity toward succinyl-CoA, since the Kd for succinyl-CoA of K221V is lower than that of the wild-type enzyme. Mutant K221V has a stronger binding affinity for succinyl-CoA compared to the wild-type enzyme. The mutation reduces the rates of quinonoid intermediate II formation and decay Mus musculus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information kinetics analysis of wild-type and mutant enzymes, single and multiple turnover and stopped flow measurements, substrate protection study, overview Mus musculus
0.001
-
 succinyl-CoA pH 7.5, 37°C, wild-type enzyme Mus musculus
0.023
-
 succinyl-CoA pH 7.5, 37°C, mutant K221V Mus musculus
8
-
 glycine pH 7.5, 37°C, wild-type enzyme Mus musculus
50
-
 glycine pH 7.5, 37°C, mutant K221V Mus musculus

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Mus musculus P08680
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant wild-type and mutant enzymes Mus musculus

Reaction

Reaction Comment Organism Reaction ID
succinyl-CoA + glycine = 5-aminolevulinate + CoA + CO2 proposed chemical mechanism of enzyme ALAS2. via (I) internal aldimine complex, (II) glycine-external aldimine, (III) quinonoid intermediate I, (IV) glycine–succinyl-CoA condensation intermediate, (V) 2-amino-3-ketoadipate intermediate, (VI) enol intermediate, (VII) quinonoid intermediate II, and (VIII) 5-aminolevulinate-external aldimine Mus musculus
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
succinyl-CoA + glycine
-
 Mus musculus 5-aminolevulinate + CoA + CO2
-
 r
succinyl-CoA + glycine it is the CoA, rather than the succinyl moiety, that facilitates binding of succinyl-CoA to wild-type ALAS Mus musculus 5-aminolevulinate + CoA + CO2
-
 r

Subunits

Subunits Comment Organism
homodimer the individual active sites are located at the dimeric interface and are composed of amino acids from each subunit Mus musculus

Synonyms

Synonyms Comment Organism
ALAS2
-
 Mus musculus
erythroid 5-aminolevulinate synthase
-
 Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Mus musculus

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.17
-
 succinyl-CoA pH 7.5, 37°C, mutant K221V Mus musculus
0.25
-
 succinyl-CoA pH 7.5, 37°C, wild-type enzyme Mus musculus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
 assay at Mus musculus

Cofactor

Cofactor Comment Organism Structure
pyridoxal 5'-phosphate dependent on Mus musculus

General Information

General Information Comment Organism
metabolism 5-aminolevulinate synthase catalyzs the initial step of mammalian heme biosynthesis Mus musculus
additional information the adenosyl-binding site Lys221 contributes to binding and orientation of succinyl-CoA for effective catalysis Mus musculus

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
7
-
 succinyl-CoA pH 7.5, 37°C, mutant K221V Mus musculus
250
-
 succinyl-CoA pH 7.5, 37°C, wild-type enzyme Mus musculus