Isoprenoid Precursor Biosynthesis in Pf apicoplasts (Plasmodium falciparum)

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2, 4, 6, 814883, 5, 9Apicoplast of Plasmodium falciparumIspHMMV008138CDP-MEPDOXPDXSCDP-MEPhosphoenolpyruvic acidGlycolysispyruvatefosmidomycinIspDPEP/Pi translocatorGlycerone-PIPPIspCTriose-P/Pi translocatorIspEDMAPPD-Glyceraldehyde 3-phosphateIspFMEP2-methyl-2-(E)-butenyl diphosphatePhosphoenolpyruvic acid7Glycerone-PHuman cellMEPCIspG


Description

This pathway shows a apicoplast of the Plasmodium falciparum that infected a human cell. The human glycolysis provides the apicoplast with nutrients for its isoprenoid precursor biosynthesis. This pathway is being investigated for targets for malaria drug leads and drugs.

Quality Tags

Ontology Terms

 

Bibliography

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  1. Yao ZK, Krai PM, Merino EF, Simpson ME, Slebodnick C, Cassera MB, Carlier PR; ''Determination of the active stereoisomer of the MEP pathway-targeting antimalarial agent MMV008138, and initial structure-activity studies.''; Bioorg Med Chem Lett, 2015 PubMed Europe PMC
  2. Yeh E, DeRisi JL; ''Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum.''; PLoS Biol, 2011 PubMed Europe PMC
  3. Borrmann S, Adegnika AA, Matsiegui PB, Issifou S, Schindler A, Mawili-Mboumba DP, Baranek T, Wiesner J, Jomaa H, Kremsner PG; ''Fosmidomycin-clindamycin for Plasmodium falciparum Infections in African children.''; J Infect Dis, 2004 PubMed Europe PMC
  4. Hunter WN; ''Isoprenoid precursor biosynthesis offers potential targets for drug discovery against diseases caused by apicomplexan parasites.''; Curr Top Med Chem, 2011 PubMed Europe PMC
  5. Ruangweerayut R, Looareesuwan S, Hutchinson D, Chauemung A, Banmairuroi V, Na-Bangchang K; ''Assessment of the pharmacokinetics and dynamics of two combination regimens of fosmidomycin-clindamycin in patients with acute uncomplicated falciparum malaria.''; Malar J, 2008 PubMed Europe PMC
  6. Wiemer AJ, Hsiao CH, Wiemer DF; ''Isoprenoid metabolism as a therapeutic target in gram-negative pathogens.''; Curr Top Med Chem, 2010 PubMed Europe PMC
  7. Wu W, Herrera Z, Ebert D, Baska K, Cho SH, DeRisi JL, Yeh E; ''A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitor targeting MEP isoprenoid precursor biosynthesis.''; Antimicrob Agents Chemother, 2015 PubMed Europe PMC
  8. Hunter WN; ''The non-mevalonate pathway of isoprenoid precursor biosynthesis.''; J Biol Chem, 2007 PubMed Europe PMC
  9. Borrmann S, Lundgren I, Oyakhirome S, Impouma B, Matsiegui PB, Adegnika AA, Issifou S, Kun JF, Hutchinson D, Wiesner J, Jomaa H, Kremsner PG; ''Fosmidomycin plus clindamycin for treatment of pediatric patients aged 1 to 14 years with Plasmodium falciparum malaria.''; Antimicrob Agents Chemother, 2006 PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
98907view14:22, 15 October 2018DeSlAdded last missing ID.
98906view14:17, 15 October 2018DeSlAdded IDs for several proteins
98890view19:47, 11 October 2018Khanspersfixed typo
98889view19:45, 11 October 2018KhanspersModified description
98888view19:44, 11 October 2018KhanspersModified title
84376view05:52, 18 February 2016EgonwOntology Term : 'PW:0000650' removed !
84375view05:51, 18 February 2016EgonwOntology Term : 'signaling pathway pertinent to development' added !
81807view15:56, 30 August 2015EgonwOK, finally got around to encoding the last bit from the paper.
81124view08:41, 25 July 2015EgonwOntology Term : 'Plasmodium infection pathway' added !
81096view08:06, 22 July 2015EgonwOntology Term : 'Plasmodium falciparum malaria' added !
81095view08:05, 22 July 2015EgonwOntology Term : 'DOID:14067' removed !
81094view08:00, 22 July 2015EgonwOntology Term : 'Plasmodium falciparum malaria' added !
81093view07:58, 22 July 2015EgonwOntology Term : 'Plasmodium falciparum malaria' added !
81092view07:53, 22 July 2015EgonwOntology Term : 'Plasmodium falciparum malaria' added !
81077view04:52, 21 July 2015EgonwAdded a disease ontology tag.
80388view18:55, 12 June 2015AlexanderPicoConnected edge and tweaked label fonts
80139view12:46, 14 May 2015EgonwIndicated the human cell embedding.
80138view12:44, 14 May 2015EgonwSet the species to Plasmodium falciparum.
80061view05:53, 4 May 2015EgonwModified description
80058view09:55, 3 May 2015EgonwModified title
80055view08:55, 3 May 2015EgonwAdded MMV008138.
80054view08:19, 3 May 2015EgonwAdded an inhibitor which has been tested for use against malaria (see 3 new references).
80053view08:11, 3 May 2015EgonwAdded (some of) the human-parasite interaction.
80052view07:45, 3 May 2015EgonwModified description
80051view07:44, 3 May 2015EgonwMore content copied in. Now a proper Human cell, with an P. falciparum acipoplast embedded in it.
80050view16:26, 2 May 2015EgonwAdded ChEBI and Entrez Gene identifiers.
80049view11:28, 2 May 2015EgonwAdded a 4th paper.
80048view11:11, 2 May 2015EgonwModified description
80047view11:10, 2 May 2015EgonwAdded two more publications.
80046view11:01, 2 May 2015EgonwNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2-methyl-2-(E)-butenyl diphosphateMetabolite
CDP-MEMetaboliteCHEBI:16578 (ChEBI) 4-Diphosphocytidyl-2-C-methylerythritol
CDP-MEPMetabolite443200 (PubChem-compound) 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate
D-Glyceraldehyde 3-phosphateMetaboliteHMDB01112 (HMDB)
DMAPPMetabolite647 (PubChem-compound) Minor product.
DOXPMetaboliteCHEBI:57792 (ChEBI) 1-deoxy-D-xylulose 5-phosphate
DXSGeneProduct813741 (Entrez Gene)
Glycerone-PMetaboliteCHEBI:16108 (ChEBI)
GlycolysisPathwayWP534 (WikiPathways)
IPPMetabolite1195 (PubChem-compound)
IspCGeneProduct812223 (Entrez Gene)
IspDGeneProductPFA0340w (Ensembl) PF3D7_0106900; PFA0340w; .7.7.60
IspEGeneProductA0A1D3U940 (Uniprot-TrEMBL)
IspFGeneProductA0A1D3RDA4 (Uniprot-TrEMBL)
IspGGeneProductQ9BJX5 (Uniprot-TrEMBL)
IspHGeneProductIPR003451 (InterPro)
MEPCMetabolite126747 (PubChem-compound) 4-Diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate
MEPMetaboliteCHEBI:58262 (ChEBI) 2C-methyl-D-erythritol 4-phosphate
MMV008138Metabolite987146 (PubChem-compound)
PEP/Pi translocatorGeneProduct813115 (Entrez Gene)
Phosphoenolpyruvic acidMetaboliteHMDB00263 (HMDB)
Triose-P/Pi translocatorGeneProduct812861 (Entrez Gene)
fosmidomycinMetabolite555 (Chemspider)
pyruvateMetaboliteCHEBI:15361 (ChEBI)

Annotated Interactions

No annotated interactions

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