About Gene List

PF3D7_0503100 (IspE)

Genome location: Pf3D7_05_v3:126,662..128,917(-)

Genome classification: Core

Function and Localization

Product Description: 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, putative

SignalP Peptide: N/A

# Transmembrane Domains: 1

EC Numbers: 2.7.1.148 (4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020011 apicoplast
Function GO:0050515 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase activity
Process GO:0008299 isoprenoid biosynthetic process

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite expressed N/A N/A
Ring possibly expressed 0.11 0.94
Trophozoite expressed 0.65 0.63
Schizont expressed 0.15 0.90
Gametocyte expressed 0.18 0.90

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0503100

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.17 | MFS: -3.264 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1102800)

  • Relative Growth Rate: 0.13 ± 0.16
  • Confidence: 5.09

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I470

"Best" AlphaFill ligand hit: No AlphaFill hits

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.1.148 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase (4Z)-4-(furan-2-ylmethylidene)-3-phenyl-1,2-oxazol-5(4H)-one(4E)-3-methyl-4-[(5-phenylfuran-2-yl)methylidene]-1,2-oxazol-5(4H)-one(4Z)-4-[(5-methylfuran-2-yl)methylidene]-3-phenyl-1,2-oxazol-5(4H)-one6-(benzylsulfanyl)-2-(2-hydroxyphenyl)-4-oxo-3,4-dihydro-2H-1,3-thiazine-5-carbonitrileN-[3-(4-amino-1-benzyl-2-oxo-1,2-dihydropyrimidin-5-yl)prop-2-en-1-yl]ethanesulfonamideN-[3-[4-amino-2-oxo-1-(tetrahydro-2-thienyl)-1,2-dihydropyrimidin-5-yl]prop-2-en-1-yl]ethanesulfonamideN-[3-[4-amino-2-oxo-1-(1H-pyrazol-5-ylmethyl)-1,2-dihydropyrimidin-5-yl]prop-2-en-1-yl]ethanesulfonamideN-[3-[4-amino-2-oxo-1-(tetrahydro-2-thienyl)-1,2-dihydropyrimidin-5-yl]prop-2-en-1-yl]methanesulfonamideN-[3-[4-amino-2-oxo-1-(tetrahydro-2-thienyl)-1,2-dihydropyrimidin-5-yl]prop-2-en-1-yl]benzenesulfonamideethyl [4-amino-2-oxo-5-(3-[[(2,2,2-trifluoroethyl)sulfonyl]amino]prop-1-en-1-yl)pyrimidin-1(2H)-yl]acetateN-[3-[4-amino-2-oxo-1-(tetrahydro-2-thienyl)-1,2-dihydropyrimidin-5-yl]prop-2-en-1-yl]propane-1-sulfonamideN-[3-[4-amino-2-oxo-1-(tetrahydro-2-thienyl)-1,2-dihydropyrimidin-5-yl]prop-2-en-1-yl]cyclopropanesulfonamide...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
Q8ZEY1 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase Yersinia pestis OrthoMCL, OrthoMCL BLAST CHEMBL493923CHEMBL1835608
P62615 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase OrthoMCL CHEMBL2289488CHEMBL3359036
P93841 4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, chloroplastic/chromoplastic OrthoMCL BLAST CHEMBL2289487

Orthology Information

Ortholog Group (OrthoMCL): OG6_106628

No human ortholog(s)

Protein Information

Protein Length: 537 | Molecular Weight (kDa): 63.376

UniProt ID(s): A0A1B1TK84, Q8I470

PDB ID(s): None

Isoelectric Point: 9.63

Protein Domain Annotations:

Source Family ID Description
InterPro IPR004424 4-diphosphocytidyl-2C-methyl-D-erythritol kinase
InterPro IPR020568 Ribosomal protein S5 domain 2-type fold
InterPro IPR036554 GHMP kinase, C-terminal domain superfamily
PFam N/A N/A
Superfamily SSF54211 Ribosomal protein S5 domain 2-type fold
Superfamily SSF55060 GHMP kinase, C-terminal domain superfamily

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 7 27 17 42
disruptive 20 57 42 103
missense 20 56 41 89

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 10 53 20 56
disruptive 27 155 82 124
missense 25 130 65 84

PlasmoDB Total SNPs: 118

Non-coding: 75 | Synonymous: 15 | Nonsynonymous: 28 | Stop Codon: 0

Associated Publications

PMID Title Authors DOI/Link
12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Hall N, Pain A, ..., Barrell BG 10.1038/nature01095
15279947 Localization of organellar proteins in Plasmodium falciparum using a novel set oftransfection vectors and a new immunofluorescence fixation method. Tonkin CJ, van Dooren GG, ..., McFadden GI 10.1016/j.molbiopara.2004.05.009
30212465 Integrative proteomics and bioinformatic prediction enable a high-confidenceapicoplast proteome in malaria parasites. Boucher MJ, Ghosh S, ..., Yeh E 10.1371/journal.pbio.2005895
38276186 Investigating Novel IspE Inhibitors of the MEP Pathway in Mycobacterium Choi SR, Narayanasamy P 10.3390/microorganisms12010018
37324717 A systematic overexpression approach reveals native targets to increase squaleneproduction in Synechocystis sp. PCC 6803 Germann AT, Nakielski A, ..., Axmann IM 10.3389/fpls.2023.1024981