About Gene List

PF3D7_0106900 (IspD)

Genome location: Pf3D7_01_v3:289,849..292,802(+)

Genome classification: Core

Function and Localization

Product Description: 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, putative

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.7.60 (2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020011 apicoplast
Function GO:0050518 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity
Process GO:0035690 cellular response to drug
Process GO:0009410 response to xenobiotic stimulus

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

Stage LR class MCA mean MCA prop. zeros
Sporozoite not expressed N/A N/A
Ring not expressed 0.06 0.97
Trophozoite possibly expressed 0.66 0.64
Schizont expressed 0.43 0.75
Gametocyte expressed 0.69 0.63

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0106900

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: 0.124 | MFS: -2.887 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0206400)

  • Relative Growth Rate: 0.10 ± 0.37
  • Confidence: 3.39

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I273

"Best" AlphaFill ligand hit: C5P (cytidine-5'-monophosphate, Local RMSD=11.23) with 1W77 (Global RMSD=15.90)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.7.60 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase CTPcefepimequercetinMMV008138rifampicintunicamycindequaliniumfosmidomycinrosuvastatinsulfanilamidechelerythrineketoclomazone...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
P69834 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase, chloroplastic OrthoMCL, OrthoMCL BLAST CHEMBL2289493CHEMBL2289491CHEMBL2289489CHEMBL2289492

Orthology Information

Ortholog Group (OrthoMCL): OG6_103820

Most Similar Human Ortholog: A0A6Q8PHI3

TM-align score: 0.54 | RMSD: 3.24

Seq Identity: 0.17 | Length: 187 / 734

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000214960 CDP-L-ribitol pyrophosphorylase A

Protein Information

Protein Length: 734 | Molecular Weight (kDa): 88.194

UniProt ID(s): A0A219YKQ2, A0A219YKQ3, Q8I273

PDB ID(s): None

Isoelectric Point: 9.89

Protein Domain Annotations:

Source Family ID Description
InterPro IPR018294 4-diphosphocytidyl-2C-methyl-D-erythritol synthase, conserved site
InterPro IPR029044 Nucleotide-diphospho-sugar transferases
InterPro IPR034683 Cytidylyltransferase IspD/TarI
PFam PF01128 Cytidylyltransferase IspD/TarI
Superfamily SSF53448 Nucleotide-diphospho-sugar transferases

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 4 28 24 48
disruptive 28 100 69 136
missense 21 79 57 115

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 7 75 37 54
disruptive 62 239 119 261
missense 36 174 93 170

PlasmoDB Total SNPs: 151

Non-coding: 65 | Synonymous: 55 | Nonsynonymous: 31 | 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
25367906 A chemical rescue screen identifies a Plasmodium falciparum apicoplast inhibitortargeting MEP isoprenoid precursor biosynthesis. Wu W, Herrera Z, ..., Yeh E 10.1128/AAC.03342-14
29958953 Deciphering the role of IspD (2_C_methyl_D_erythritol 4_phosphatecytidyltransferase) enzyme as a potential therapeutic drug target againstPlasmodium vivax. Saggu GS, Garg S, ..., Saxena V 10.1016/j.gene.2018.06.084
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
38305785 Crystal structure and biophysical characterization of IspD from Burkholderiathailandensis and Mycobacterium paratuberculosis Pierce PG, Hartnett BE, ..., Myler PJ 10.1107/S2053230X24000621