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Literature summary for 2.6.1.44 extracted from

  • Dindo, M.; Mandrile, G.; Conter, C.; Montone, R.; Giachino, D.; Pelle, A.; Costantini, C.; Cellini, B.
    The ILE56 mutation on different genetic backgrounds of alanine glyoxylate aminotransferase clinical features and biochemical characterization (2020), Mol. Genet. Metab., 131, 171-180 .
No PubMed abstract available

Cloned(Commentary)

Cloned (Comment) Organism
gene AGXT, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 Homo sapiens

Protein Variants

Protein Variants Comment Organism
I56N site-directed mutagenesis, the Ile56Asn mutation induces a structural defect mostly related to the apo-form of enzyme AGT. The effects are more pronounced when the substitution of Ile56 is combined with the Pro11Leu and, at higher degree, the Pro11Arg mutation Homo sapiens
additional information biochemical properties of Pro11 and Ile56 variants: secondary, tertiary, and quaternary structures, overview Homo sapiens
P11L naturally occuring polymorphic mutation Homo sapiens
P11L/I56N site-directed mutagenesis, the Ile56Asn mutation induces a structural defect mostly related to the apo-form of enzyme AGT. The effects are more pronounced when the substitution of Ile56 is combined with the Pro11Leu and, at higher degree, the Pro11Arg mutation Homo sapiens
P11R naturally occuring pathogenic mutation Homo sapiens
P11R/I56N site-directed mutagenesis, the Ile56Asn mutation induces a structural defect mostly related to the apo-form of enzyme AGT. The effects are more pronounced when the substitution of Ile56 is combined with the Pro11Leu and, at higher degree, the Pro11Arg mutation Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.22
-
glyoxylate recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
0.23
-
glyoxylate recombinant mutant I56N-Ma, pH 7.4, 25°C Homo sapiens
0.23
-
glyoxylate recombinant wild-type enzyme AGT-Ma, pH 7.4, 25°C Homo sapiens
0.6
-
glyoxylate recombinant mutant I56N-Mi, pH 7.4, 25°C Homo sapiens
0.88
-
glyoxylate recombinant mutant P11R/I56N-Ma, pH 7.4, 25°C Homo sapiens
1
-
glyoxylate recombinant mutant P11R-Ma, pH 7.4, 25°C Homo sapiens
28
-
L-alanine recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
31
-
L-alanine recombinant wild-type enzyme AGT-Ma, pH 7.4, 25°C Homo sapiens
37
-
L-alanine recombinant mutant P11R-Ma, pH 7.4, 25°C Homo sapiens
43
-
L-alanine recombinant mutant I56N-Mi, pH 7.4, 25°C Homo sapiens
59
-
L-alanine recombinant mutant I56N-Ma, pH 7.4, 25°C Homo sapiens
80
-
L-alanine recombinant mutant P11R/I56N-Ma, pH 7.4, 25°C Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-alanine + glyoxylate Homo sapiens
-
pyruvate + glycine
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P21549
-
-

Source Tissue

Source Tissue Comment Organism Textmining
kidney
-
Homo sapiens
-
liver
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-alanine + glyoxylate
-
Homo sapiens pyruvate + glycine
-
?

Subunits

Subunits Comment Organism
More biochemical properties of Pro11 and Ile56 variants: secondary, tertiary, and quaternary structures, overview Homo sapiens

Synonyms

Synonyms Comment Organism
AGT
-
Homo sapiens
AGXT
-
Homo sapiens
alanine: glyoxylate aminotransferase
-
Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
18
-
L-alanine recombinant mutant I56N-Mi, pH 7.4, 25°C Homo sapiens
19
-
L-alanine recombinant mutant P11R/I56N-Ma, pH 7.4, 25°C Homo sapiens
22
-
glyoxylate recombinant mutant I56N-Mi, pH 7.4, 25°C Homo sapiens
22
-
L-alanine recombinant mutant P11R-Ma, pH 7.4, 25°C Homo sapiens
22
-
glyoxylate recombinant mutant P11R/I56N-Ma, pH 7.4, 25°C Homo sapiens
23
-
glyoxylate recombinant mutant P11R-Ma, pH 7.4, 25°C Homo sapiens
29
-
L-alanine recombinant mutant I56N-Ma, pH 7.4, 25°C Homo sapiens
30
-
glyoxylate recombinant mutant I56N-Ma, pH 7.4, 25°C Homo sapiens
33
-
glyoxylate recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
37
-
L-alanine recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
45
-
glyoxylate recombinant wild-type enzyme AGT-Ma, pH 7.4, 25°C Homo sapiens
45
-
L-alanine recombinant wild-type enzyme AGT-Ma, pH 7.4, 25°C 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 PLP Homo sapiens

General Information

General Information Comment Organism
evolution enzyme AGT is present in the human population in two allelic forms, the major allele encoding AGT-Ma and the minor allele encoding AGT-Mi, the latter characterized by the Pro11 to Leu and Ile340 to Met amino acid substitutions Homo sapiens
malfunction primary hyperoxaluria type I (PH1) is a rare disease caused by mutations in the AGXT gene encoding alanine:glyoxylate aminotransferase (AGT), a liver enzyme involved in the detoxification of glyoxylate, the failure of which results in accumulation of oxalate and kidney stones formation. The role of protein misfolding in the AGT deficit caused by most PH1-causing mutations. Analysis of the clinical, biochemical and cellular effects of the p.Ile56Asn mutation, recently described in a PH1 patient, as a function of the residue at position 11, a hot-spot for both polymorphic (p.Pro11Leu) and pathogenic (p.Pro11Arg) mutations, overview. As compared with the non-pathogenic forms, AGT variants display reduced expression and activity in mammalian cells. Vitamin B6, a currently approved treatment for PH1, can overcome the effects of the p.Ile56Asn mutation only when it is associated with Pro at position 11. Primary hyperoxaluria type I (PH1), the most severe form of primary hyperoxaluria, is an inherited condition characterized by an increased endogenous production of oxalate, a metabolic end-product excreted by urine, that leads to the formation and precipitation of calcium oxalate crystals, first in the kidneys and urinary tract and then in many tissues including skin, bones, heart and retina, a condition known as systemic oxalosis Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.24
-
L-alanine recombinant mutant P11R/I56N-Ma, pH 7.4, 25°C Homo sapiens
0.42
-
L-alanine recombinant mutant I56N-Mi, pH 7.4, 25°C Homo sapiens
0.49
-
L-alanine recombinant mutant I56N-Ma, pH 7.4, 25°C Homo sapiens
0.6
-
L-alanine recombinant mutant P11R-Ma, pH 7.4, 25°C Homo sapiens
1.32
-
L-alanine recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
1.45
-
L-alanine recombinant wild-type enzyme AGT-Ma, pH 7.4, 25°C Homo sapiens
23
-
glyoxylate recombinant mutant P11R-Ma, pH 7.4, 25°C Homo sapiens
25
-
glyoxylate recombinant mutant P11R/I56N-Ma, pH 7.4, 25°C Homo sapiens
36.6
-
glyoxylate recombinant mutant I56N-Mi, pH 7.4, 25°C Homo sapiens
130.4
-
glyoxylate recombinant mutant I56N-Ma, pH 7.4, 25°C Homo sapiens
150
-
glyoxylate recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
195.7
-
glyoxylate recombinant wild-type enzyme AGT-Ma, pH 7.4, 25°C Homo sapiens