Cloned (Comment) | Organism |
---|---|
gene AGXT, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21 | Homo sapiens |
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 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 | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-alanine + glyoxylate | Homo sapiens | - |
pyruvate + glycine | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P21549 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
kidney | - |
Homo sapiens | - |
liver | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-alanine + glyoxylate | - |
Homo sapiens | pyruvate + glycine | - |
? |
Subunits | Comment | Organism |
---|---|---|
More | biochemical properties of Pro11 and Ile56 variants: secondary, tertiary, and quaternary structures, overview | Homo sapiens |
Synonyms | Comment | Organism |
---|---|---|
AGT | - |
Homo sapiens |
AGXT | - |
Homo sapiens |
alanine: glyoxylate aminotransferase | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Homo sapiens |
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 Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
pyridoxal 5'-phosphate | PLP | Homo sapiens |
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 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 |