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Literature summary for 2.6.1.44 extracted from

  • Dindo, M.; Montioli, R.; Busato, M.; Giorgetti, A.; Cellini, B.; Borri Voltattorni, C.
    Effects of interface mutations on the dimerization of alanine glyoxylate aminotransferase and implications in the mistargeting of the pathogenic variants F152I and I244T (2016), Biochimie, 131, 137-148 .
    View publication on PubMed
Search for more literature for 2.6.1.44

Protein Variants

Protein Variants Comment Organism
F238S site-directed mutagenesis Homo sapiens
F240S site-directed mutagenesis Homo sapiens
additional information molecular dynamics simulations of F152I-Mi and I244T-Mi variants associated with PH1 and implications in their pathogenicity Homo sapiens
R118A site-directed mutagenesis Homo sapiens
R118A/F238S/F240S site-directed mutagenesis, the apo and the holo forms of the triple mutant R118A-Mi/F238S-Mi/F240S-Mi display a dimer-monomer equilibrium dissociation constant value at least about 260 and 31fold larger, respectively, than the corresponding ones of wild-type AGT-Mi. In the presence of cofactor pyridoxala 5'-phosphate (PLP), the apo-monomer of the triple mutant undergoes a biphasic process: the fast phase represents the formation of an inactive PLP-bound monomer, while the slow phase depicts the monomer-monomer association that parallels the regain of transaminase activity. The latter events occur with a rate constant of about 20 nM/min. In the absence of PLP, the apomonomer is also able to dimerize but with a rate constant value about 2700fold lower. Kinetics of dimerization of triple variant, overview Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information steady-state kinetics of wild-type and mutant enzymes Homo sapiens
0.18
-
 glyoxylate recombinant mutant R118A, pH 7.4, 25°C Homo sapiens
0.2
-
 glyoxylate recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
0.28
-
 glyoxylate recombinant mutant F240S, pH 7.4, 25°C Homo sapiens
0.71
-
 glyoxylate recombinant mutant F238S, pH 7.4, 25°C Homo sapiens
46
-
 L-alanine recombinant mutant F238S, pH 7.4, 25°C Homo sapiens
51
-
 L-alanine recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
77
-
 L-alanine recombinant mutant R118A, pH 7.4, 25°C Homo sapiens
84
-
 L-alanine recombinant mutant F240S, pH 7.4, 25°C Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
peroxisome
-
 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
monomer or dimer the enzyme displays a a dimer-monomer equilibrium Homo sapiens
More Arg118, Phe238 and Phe240 are interfacial residues not essential for transaminase activity but important for dimer-monomer dissociation. AGT dimer interface model, overview. A synergic role of the residues Arg118 and Phe240 exist on the formation of the dimer of AGT-Mi, and substitution of both Phe238 and Phe240 with Ser might be relevant in preventing monomer-monomer aggregation. Proposed folding and dimerization pathway of wild-type AGT-Mi and of mutant I244T-Mi and F152T-Mi variant, overviews 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

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
3 6 L-alanine recombinant mutant F238S, pH 7.4, 25°C Homo sapiens
19
-
 glyoxylate recombinant mutant R118A, pH 7.4, 25°C Homo sapiens
20
-
 glyoxylate recombinant mutant F240S, pH 7.4, 25°C Homo sapiens
21
-
 L-alanine recombinant mutant R118A, pH 7.4, 25°C Homo sapiens
22
-
 L-alanine recombinant mutant F240S, pH 7.4, 25°C Homo sapiens
35
-
 glyoxylate recombinant mutant F238S, pH 7.4, 25°C Homo sapiens
35
-
 L-alanine recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
39
-
 glyoxylate recombinant wild-type enzyme AGT-Mi, 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 binding analysis with monomeric and dimeric enzyme, overview 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 deficit of AGT causes primary hyperoxaluria type I (PH1) (OMIM 259900), a rare metabolic recessive disease due to inborn errors affecting the metabolism of glyoxylate in liver peroxisomes. Molecular dynamics simulations of F152I-Mi and I244T-Mi variants associated with PH1 and implications in their pathogenicity Homo sapiens
additional information Arg118, Phe238 and Phe240 are interfacial residues not essential for transaminase activity but important for dimer-monomer dissociation. Molceular dynamics simulations Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.26
-
 L-alanine recombinant mutant F240S, pH 7.4, 25°C Homo sapiens
0.27
-
 L-alanine recombinant mutant R118A, pH 7.4, 25°C Homo sapiens
0.69
-
 L-alanine recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens
0.78
-
 L-alanine recombinant mutant F238S, pH 7.4, 25°C Homo sapiens
49.3
-
 glyoxylate recombinant mutant F238S, pH 7.4, 25°C Homo sapiens
71.4
-
 glyoxylate recombinant mutant F240S, pH 7.4, 25°C Homo sapiens
105.6
-
 glyoxylate recombinant mutant R118A, pH 7.4, 25°C Homo sapiens
195
-
 glyoxylate recombinant wild-type enzyme AGT-Mi, pH 7.4, 25°C Homo sapiens