Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Tjhin, E.T.; Spry, C.; Sewell, A.L.; Hoegl, A.; Barnard, L.; Sexton, A.E.; Siddiqui, G.; Howieson, V.M.; Maier, A.G.; Creek, D.J.; Strauss, E.; Marquez, R.; Auclair, K.; Saliba, K.J.
    Mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues (2018), PLoS Pathog., 14, e1006918 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

EC Number Protein Variants Comment Organism
2.7.1.33 additional information parasites pressured with pantothenol or CJ-15,801 become resistant to these antiplasmodial pantothenate analogues. Pfpank1 mutations mediate parasite resistance to PanOH and CJ-15,801. Whole-genome sequencing reveals mutations in one of two putative PanK genes (Pfpank1) in each resistant line. These mutations significantly alter PfPanK activity, with two conferring a fitness cost, consistent with Pfpank1 coding for a functional PanK that is essential for normal growth. Pfpank1 disruption plasmid, DELTAPfpank1-pCC-1 (SI), is transfected into wild-type Palsmodium falciparum strain 3D7 Plasmodium falciparum

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.7.1.33 (2E)-3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]prop-2-enoic acid
-
 Plasmodium falciparum

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.7.1.33 Mg2+ required Plasmodium falciparum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.7.1.33 ATP + (R)-pantothenate Plasmodium falciparum
-
 ADP + (R)-4'-phosphopantothenate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.7.1.33 Plasmodium falciparum Q8ILP4
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.7.1.33 trophozoite
-
 Plasmodium falciparum
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.7.1.33 ATP + (R)-pantothenate
-
 Plasmodium falciparum ADP + (R)-4'-phosphopantothenate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.7.1.33 PanK
-
 Plasmodium falciparum
2.7.1.33 pantothenate kinase 1 UniProt Plasmodium falciparum
2.7.1.33 PfPanK
-
 Plasmodium falciparum
2.7.1.33 Pfpank1
-
 Plasmodium falciparum

General Information

EC Number General Information Comment Organism
2.7.1.33 malfunction mutations in the pantothenate kinase of Plasmodium falciparum confer diverse sensitivity profiles to antiplasmodial pantothenate analogues. Pfpank1 mutations mediate parasite resistance to PanOH and CJ-15,801. Parasites pressured with pantothenol or (2E)-3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]prop-2-enoic acid (CJ-15,801) become resistant to these antiplasmodial pantothenate analogues. Whole-genome sequencing reveals mutations in one of two putative PanK genes (Pfpank1) in each resistant line. These mutations significantly alter PfPanK activity, with two conferring a fitness cost, consistent with Pfpank1 coding for a functional PanK that is essential for normal growth. Different pantothenate analogue classes have different mechanisms of action: some inhibit CoA biosynthesis while others inhibit CoA-utilising enzymes Plasmodium falciparum
2.7.1.33 additional information the structure of PfPanK1 minus its parasite-specific inserts is predicted by homology modeling using the AMPPNP and pantothenate-bound human PanK3 structure (PDB ID 5KPR) as a template. PfPanK1 shares 28% sequence identity with human PanK3 over the protein parts that are modeled Plasmodium falciparum
2.7.1.33 physiological function the malaria-causing blood stage of Plasmodium falciparum requires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Pfpank1 coding for a functional PanK that is essential for normal growth. Plasmodium falciparum parasites have previously been shown to survive equally well in a pantothenate-free complete RPMI 1640 medium supplemented with 0.1 mM CoA as compared to standard complete medium, consistent with them having the capacity to take up exogenous CoA, hence bypassing the need for any PfPanK activity Plasmodium falciparum