Protein Variants | Comment | Organism |
---|---|---|
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 | Comment | Organism | Structure |
---|---|---|---|
(2E)-3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]prop-2-enoic acid | - |
Plasmodium falciparum |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Plasmodium falciparum |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + (R)-pantothenate | Plasmodium falciparum | - |
ADP + (R)-4'-phosphopantothenate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Plasmodium falciparum | Q8ILP4 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
trophozoite | - |
Plasmodium falciparum | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + (R)-pantothenate | - |
Plasmodium falciparum | ADP + (R)-4'-phosphopantothenate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
PanK | - |
Plasmodium falciparum |
pantothenate kinase 1 | UniProt | Plasmodium falciparum |
PfPanK | - |
Plasmodium falciparum |
Pfpank1 | - |
Plasmodium falciparum |
General Information | Comment | Organism |
---|---|---|
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 |
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 |
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 |