Literature summary for 2.6.1.44 extracted from

Dindo, M.; Oppici, E.; DellOrco, D.; Montone, R.; Cellini, B.
Correlation between the molecular effects of mutations at the dimer interface of alanine-glyoxylate aminotransferase leading to primary hyperoxaluria type I and the cellular response to vitamin B6 (2018), J. Inherit. Metab. Dis., 41, 263-275 .

Search for more literature for 2.6.1.44

Cloned(Commentary)

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

Protein Variants

Protein Variants	Comment	Organism
G216R	site-directed mutagenesis, the mutant displays structural alterations mainly related to the apoform and consisting of an altered tertiary and quaternary structure, it also shows a strongly reduced catalytic efficiency	Homo sapiens
G42E	site-directed mutagenesis, the mutant displays structural alterations mainly related to the apoform and consisting of an altered tertiary and quaternary structure	Homo sapiens
G63R	site-directed mutagenesis, the mutant displays structural alterations mainly related to the apoform and consisting of an altered tertiary and quaternary structure	Homo sapiens
I56N	site-directed mutagenesis, the mutant displays structural alterations mainly related to the apoform and consisting of an altered tertiary and quaternary structure. The I56N mutation destabilizes the apo-WT-AGT quaternary structure, an effect possibly caused by the substitution of Ile56 to ASN interferes with interchain hydrophobic interactions between Ile56 and Leu18 and Ile20 of the other subunit	Homo sapiens
additional information	analysis of the effects of pathogenic interfacial mutations by combining bioinformatic predictions with molecular and cellular studies on selected variants (R36H, G42E, I56N, G63R, and G216R) in both their holo- (i.e. with bound PLP) and apo- (i.e. without bound PLP) form. All variants display structural alterations mainly related to the apoform and consisting of an altered tertiary and quaternary structure. Possible inverse correlation between the degree of destabilization/misfolding induced by a mutation and the extent of B6 responsiveness. More than 150 pathogenic mutations on the AGXT gene have been identified to date. Structure-function analysis of wild-type and mutant enzymes, overview	Homo sapiens
R36H	site-directed mutagenesis, the mutant displays structural alterations mainly related to the apoform and consisting of an altered tertiary and quaternary structure	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
peroxisome	AGT is synthetized and folded in the cell cytosol before being imported into peroxisomes via the interaction with the Pex5p carrier	Homo sapiens	5777	-

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
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
homodimer	structure modeling with monomer-monomer interface and active site, overview	Homo sapiens
More	dimerization is considered a crucial event, because it is supposed to influence the overall stability of the protein as well as its intracellular fate, including, in particular, the correct peroxisomal localization. Rigid-body protein-protein docking simulations aiming at predicting and analyzing the quaternary structure of proteins using the structure of dimeric AGT in complex with the tetratricopeptide repeat (TPR) domain of human Pex5p (PDB ID 3R9A), overview	Homo sapiens

Synonyms

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

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
25	-	assay at	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	cofactor binding and kinetics of wild-type and mutant enzymes, overview. Stabilizing effect of PLP binding is mediated by the loop Gly252-Val266, which faces the active site and could be maintained by the coenzyme in the correct conformation. Pyridoxal 5'-phosphate (PLP) exerts a chaperone role by promoting dimerization	Homo sapiens

General Information

General Information	Comment	Organism
evolution	AGT is a homodimer and belongs to the fold type I family of PLP-dependent enzymes. 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	possible inverse correlation between the degree of destabilization/misfolding induced by a mutation and the extent of vitamin B6 responsiveness in PH1. Among the 79 missense mutations known to be associated with PH1, 26 involve residues directly located at the monomer-monomer interface	Homo sapiens
additional information	the overall transamination catalyzed by AGT follows a ping-pong mechanism	Homo sapiens
physiological function	primary hyperoxaluria type I (PH1) is a rare disease caused by the deficit of liver alanine-glyoxylate aminotransferase (AGT). AGT prevents oxalate formation by converting peroxisomal glyoxylate to glycine. When the enzyme is deficient, progressive calcium oxalate stones deposit first in the urinary tract and then at the systemic level. Pyridoxal 5'-phosphate (PLP), the AGT coenzyme, exerts a chaperone role by promoting dimerization	Homo sapiens

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Release 2023.1 (January 2023)