Literature summary for 2.7.1.35 extracted from

Gao, K.; Wang, W.; Kronenberger, T.; Wrenger, C.; Groves, M.
The crystal structure of the Plasmodium falciparum PdxK provides an experimental model for pro-drug activation (2019), Crystals, 9, 534 .

No PubMed abstract available

Cloned(Commentary)

Cloned (Comment)	Organism
gene pdxK, sequence comparisons, recombinant expression of His-tagged enzyme in Escherichia coli strain Rosetta 2 (DE3)	Plasmodium falciparum

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme in apoform and in complex with AMP-PNP and pyridoxal (PL), hanging drop vapour diffusion method, for apoform mixing of protein solution with reservoir solution containing 0.1 M HEPES, pH 7.75, 0.2 M CaCl2, 31% v/v PEG 400, and 5% v/v glycerol, and soaking of crystals in solution with 5 mM ligand, at 20°C, X-ray diffraction structure determination and analysis at 2.15 A resolution, molecular replacement using the the coordinates of PdxK from sheep brain as a search model (PDB ID 1RFU), and modelling. The fold is retained and both AMP-PNP and PL occupy the same binding sites when compared to the human orthologue	Plasmodium falciparum

Crystallization (Comment)

Organism

purified enzyme in apoform and in complex with AMP-PNP and pyridoxal (PL), hanging drop vapour diffusion method, for apoform mixing of protein solution with reservoir solution containing 0.1 M HEPES, pH 7.75, 0.2 M CaCl2, 31% v/v PEG 400, and 5% v/v glycerol, and soaking of crystals in solution with 5 mM ligand, at 20°C, X-ray diffraction structure determination and analysis at 2.15 A resolution, molecular replacement using the the coordinates of PdxK from sheep brain as a search model (PDB ID 1RFU), and modelling. The fold is retained and both AMP-PNP and PL occupy the same binding sites when compared to the human orthologue

Plasmodium falciparum

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Plasmodium falciparum

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + pyridoxal	Plasmodium falciparum	-	ADP + pyridoxal 5'-phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Plasmodium falciparum	C6KT01	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain Rosetta 2 (DE3) by nickel affinity chromatography and gel filtration	Plasmodium falciparum

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
ATP + methyl (1S)-1-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate	-	Plasmodium falciparum	ADP + methyl (1S)-1-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 5'-phosphate	-	?
ATP + methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]histidinate	-	Plasmodium falciparum	ADP + methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]histidinate 5'-phosphate	-	?
ATP + methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]tryptophanate	-	Plasmodium falciparum	ADP + methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]tryptophanate 5'-phosphate	-	?
ATP + pyridoxal	-	Plasmodium falciparum	ADP + pyridoxal 5'-phosphate	-	?
additional information	docking analysis of potent antimalarials to the enzyme, molecular docking indicates potential binding modes of methyl (1S)-1-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate, methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]tryptophanate, and methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]histidinate as substrates of PfPdxK. PfPdxK is strongly implicated in the phosphorylation of methyl (1S)-1-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate, methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]tryptophanate, and methyl N-[[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl]methyl]histidinate into their active forms	Plasmodium falciparum	?	-	-

Synonyms

Synonyms	Comment	Organism
PdxK	-	Plasmodium falciparum

General Information

General Information	Comment	Organism
evolution	pyridoxine/pyridoxal kinase (PdxK) belongs to the ribokinase family and is involved in the vitamin B6 salvage pathway by phosphorylating pyridoxal (PL) into an active form. In the human malaria parasite, Plasmodium falciparum, PfPdxK functions to salvage vitamin B6 from both itself and its host	Plasmodium falciparum
additional information	a FIxxIIxL motif at the C-terminus of the disordered repeat motif (XNXH)m that is implicated in binding the WD40 domain and may provide temporal control of PfPdxK through an interaction with a E3 ligase complex. Molecular docking and modelling, overview. Binding structure of AMP-PNP with PdxK	Plasmodium falciparum
physiological function	pyridoxine/pyridoxal kinase (PdxK) belongs to the ribokinase family and is involved in the vitamin B6 salvage pathway by phosphorylating pyridoxal (PL) into an active form. In the human malaria parasite, Plasmodium falciparum, PfPdxK functions to salvage vitamin B6 from both itself and its host	Plasmodium falciparum