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Literature summary extracted from

  • Mascolo, E.; Barile, A.; Mecarelli, L.S.; Amoroso, N.; Merigliano, C.; Massimi, A.; Saggio, I.; Hansen, T.; Tramonti, A.; Di Salvo, M.L.; Barbetti, F.; Contestabile, R.; Verni, F.
    The expression of four pyridoxal kinase (PDXK) human variants in Drosophila impacts on genome integrity (2019), Sci. Rep., 9, 14188 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.7.1.35 gene PDXK, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta(lambdaDE3) pLysS Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.35 A243G naturally occuring mutation from a patient with diabetes, the mutant shows reduced catalytic activity and/or reduced affinity for PLP precursors, the mutant cannot complement the inactive Drosophila melanogaster dPdxk1 mutant when expressed in the mutant flies. Mutant A243G displays a damaging score of 0.72. The A243Q mutation somewhat reduces the affinity for ATP when using PL as substrate and the affinity for PM, while it does not affect KM for PL and PN. In addition, it has the effect to halve kcat with PL Homo sapiens
2.7.1.35 D87H naturally occuring mutation, the mutant shows reduced catalytic activity and/or reduced affinity for PLP precursors, the mutant cannot complement the inactive Drosophila melanogaster dPdxk1 mutant when expressed in the mutant flies. Mutant D87H displays the highest damaging score (1.0). The D87H mutation strongly increases KM for PL, and to a lesser extent also increases KM for PN and PM, leaving KM for ATP and kcat almost unaltered Homo sapiens
2.7.1.35 H246Q naturally occuring mutation, the mutant shows reduced catalytic activity and/or reduced affinity for PLP precursors, the mutant cannot complement the inactive Drosophila melanogaster dPdxk1 mutant when expressed in the mutant flies. Mutant H246Q displays a damaging score of 0.98. The H246Q mutation somewhat reduces the affinity for ATP when using PL as substrate and the affinity for PM, while it does not affect KM for PL and PN. In addition, it has the effect to halve kcat with PL Homo sapiens
2.7.1.35 additional information in Drosophila, mutations in the dPdxk gene cause chromosome aberrations (CABs) and increased glucose content in larval hemolymph. The hyperglycemia phenotype is rescued by the expression of wild-type human PDXK enzyme, although not by human PDXK mutants D87H, V128I, H246Q, and A243G. To introduce the transgenes carrying the PDXK variants (PDXK VAR) in a mutant dPdxk1 background, the PDXKVAR/CyGFP, MKRS/TM6B females to CyGFP/Sco, dPdxk1/TM6B males are crossed. The progeny of this cross, PDXKVAR /CyGFP, dPdxk1/TM6B, is crossed inter se to obtain a stable stock Drosophila melanogaster
2.7.1.35 V128I naturally occuring mutation, the mutant shows reduced catalytic activity and/or reduced affinity for PLP precursors, the mutant cannot complement the inactive Drosophila melanogaster dPdxk1 mutant when expressed in the mutant flies. Mutant V128I isplays a damaging score of 0.99. The V128I mutation drastically increases KM for PL and KM for ATP with this vitamer, whereas it does not affect kcat Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.7.1.35 0.141
-
 pyridoxal pH 7.3, 37°C recombinant mutant H246Q Homo sapiens
2.7.1.35 0.177
-
 pyridoxal pH 7.3, 37°C recombinant mutant A243G Homo sapiens
2.7.1.35 0.189
-
 pyridoxal pH 7.3, 37°C recombinant wild-type enzyme Homo sapiens
2.7.1.35 0.377
-
 ATP pH 7.3, 37°C recombinant mutant D87H Homo sapiens
2.7.1.35 0.407
-
 ATP pH 7.3, 37°C recombinant wild-type enzyme Homo sapiens
2.7.1.35 0.901
-
 ATP pH 7.3, 37°C recombinant mutant H246Q Homo sapiens
2.7.1.35 1.024
-
 ATP pH 7.3, 37°C recombinant mutant A243G Homo sapiens
2.7.1.35 2.09
-
 pyridoxal pH 7.3, 37°C recombinant mutant D87H Homo sapiens
2.7.1.35 3.096
-
 ATP pH 7.3, 37°C recombinant mutant V128I Homo sapiens
2.7.1.35 3.839
-
 pyridoxal pH 7.3, 37°C recombinant mutant V128I Homo sapiens

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.35 Mg2+ required Homo sapiens
2.7.1.35 Mg2+ required Drosophila melanogaster

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.35 ATP + pyridoxal Homo sapiens
-
 ADP + pyridoxal 5'-phosphate
-
 ?
2.7.1.35 ATP + pyridoxal Drosophila melanogaster
-
 ADP + pyridoxal 5'-phosphate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.35 Drosophila melanogaster Q7KUC2
-
-
2.7.1.35 Homo sapiens O00764
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.35 brain
-
 Drosophila melanogaster
-
2.7.1.35 HeLa cell
-
 Homo sapiens
-
2.7.1.35 larva
-
 Drosophila melanogaster
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.35 ATP + pyridoxal
-
 Homo sapiens ADP + pyridoxal 5'-phosphate
-
 ?
2.7.1.35 ATP + pyridoxal
-
 Drosophila melanogaster ADP + pyridoxal 5'-phosphate
-
 ?

Subunits

EC Number Subunits Comment Organism
2.7.1.35 homodimer PDXK is a dimer of two identical monomers. Each subunit is made by 9 alpha-helices and 11 beta-strands that form a central beta-sheet flanked by helices on both sides. Asp87 is placed on the C-terminal end of an active site loop connecting alpha3 helix and strand beta4, which plays a crucial role in substrate binding. Tyr84, which is part of this loop, directly interacts with the B6 vitamer substrate stacking to its pyridine ring, see for PDB ID 3KEU Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
2.7.1.35 PdxK
-
 Homo sapiens
2.7.1.35 PdxK
-
 Drosophila melanogaster

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
2.7.1.35 37
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.7.1.35 0.47
-
 ATP pH 7.3, 37°C recombinant mutant A243G Homo sapiens
2.7.1.35 0.47
-
 pyridoxal pH 7.3, 37°C recombinant mutant A243G Homo sapiens
2.7.1.35 0.58
-
 ATP pH 7.3, 37°C recombinant mutant H246Q Homo sapiens
2.7.1.35 0.58
-
 pyridoxal pH 7.3, 37°C recombinant mutant H246Q Homo sapiens
2.7.1.35 0.67
-
 ATP pH 7.3, 37°C recombinant mutant D87H Homo sapiens
2.7.1.35 0.67
-
 pyridoxal pH 7.3, 37°C recombinant mutant D87H Homo sapiens
2.7.1.35 0.97
-
 ATP pH 7.3, 37°C recombinant wild-type enzyme Homo sapiens
2.7.1.35 0.97
-
 pyridoxal pH 7.3, 37°C recombinant wild-type enzyme Homo sapiens
2.7.1.35 1.12
-
 ATP pH 7.3, 37°C recombinant mutant V128I Homo sapiens
2.7.1.35 1.12
-
 pyridoxal pH 7.3, 37°C recombinant mutant V128I Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.7.1.35 7.3
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
2.7.1.35 malfunction in Drosophila, mutations in the dPdxk gene cause chromosome aberrations (CABs) and increased glucose content in larval hemolymph. The phenotype is rescued by the expression of wild-type human PDXK enzyme, although not by human PDXK mutants D87H, V128I, H246Q, and A243G Drosophila melanogaster
2.7.1.35 malfunction the four PDXK human variants, D87H, V128I, H246Q, and A243Gf D87H, V128I, H246Q and A243G proteins show reduced catalytic activity and/or reduced affinity for PLP precursors. Although these variants are rare in population and carried in heterozygous condition, it is suggested that in certain metabolic contexts and diseases in which PLP levels are reduced, the presence of these PDXK variants might threaten genome integrity and increase cancer risk Homo sapiens
2.7.1.35 physiological function in eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B6 salvage pathway to produce pyridoxal 5'-phosphate (PLP), the active form of the vitamin, which is implicated in numerous crucial metabolic reactions. PDXK converts PLP precursors such as pyridoxal (PL), pyridoxamine (PM) and pyridoxine (PN) taken from food into PLP, PMP and PNP, respectively. PNPO catalyzes the oxidation of PMP and PNP into PLP. PLP performs many functions by working as coenzyme for a wide number of enzymes which control amino acid, lipid and carbohydrate metabolism Homo sapiens
2.7.1.35 physiological function in eukaryotes, pyridoxal kinase (PDXK) acts in vitamin B6 salvage pathway to produce pyridoxal 5'-phosphate (PLP), the active form of the vitamin, which is implicated in numerous crucial metabolic reactions. PDXK converts PLP precursors such as pyridoxal (PL), pyridoxamine (PM) and pyridoxine (PN) taken from food into PLP, PMP and PNP, respectively. PNPO catalyzes the oxidation of PMP and PNP into PLP. PLP performs many functions by working as coenzyme for a wide number of enzymes which control amino acid, lipid and carbohydrate metabolism Drosophila melanogaster

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
2.7.1.35 0.29
-
 pyridoxal pH 7.3, 37°C recombinant mutant V128I Homo sapiens
2.7.1.35 0.32
-
 pyridoxal pH 7.3, 37°C recombinant mutant D87H Homo sapiens
2.7.1.35 0.36
-
 ATP pH 7.3, 37°C recombinant mutant V128I Homo sapiens
2.7.1.35 0.46
-
 ATP pH 7.3, 37°C recombinant mutant A243G Homo sapiens
2.7.1.35 0.64
-
 ATP pH 7.3, 37°C recombinant mutant H246Q Homo sapiens
2.7.1.35 1.78
-
 ATP pH 7.3, 37°C recombinant mutant D87H Homo sapiens
2.7.1.35 2.38
-
 ATP pH 7.3, 37°C recombinant wild-type enzyme Homo sapiens
2.7.1.35 2.66
-
 pyridoxal pH 7.3, 37°C recombinant mutant A243G Homo sapiens
2.7.1.35 4.11
-
 pyridoxal pH 7.3, 37°C recombinant mutant H246Q Homo sapiens
2.7.1.35 5.13
-
 pyridoxal pH 7.3, 37°C recombinant wild-type enzyme Homo sapiens