About Gene List

PF3D7_1121900 (PDK1)

Genome location: Pf3D7_11_v3:835,823..837,872(-)

Genome classification: Core

Function and Localization

Product Description: 3-phosphoinositide-dependent protein kinase 1

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.11.1 (Non-specific serine/threonine protein kinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005829 cytosol
Component GO:0005634 nucleus
Function GO:0004672 protein kinase activity
Function GO:0004674 protein serine/threonine kinase activity
Process GO:0032147 activation of protein kinase activity
Process GO:0035556 intracellular signal transduction
Process GO:0018105 peptidyl-serine phosphorylation
Process GO:0006468 protein phosphorylation
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 0.02 0.99
Trophozoite expressed 0.21 0.87
Schizont expressed 0.20 0.87
Gametocyte expressed 0.22 0.87

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1121900

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: 0.249 | MFS: -3.434 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IIE7

"Best" AlphaFill ligand hit: DTD (dithiane diol, Local RMSD=0.77) with 4AW0 (Global RMSD=4.46)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.11.1 non-specific serine/threonine protein kinase ATPKClDTTP53DRBEDTATBCAKN-93K252aCKI-7LAALSTAACS...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
O15530 3-phosphoinositide-dependent protein kinase 1 Homo sapiens OrthoDB Indazole Compound 1Indazole Compound 2Debromohymenialdisine (DBH)BX-201...

Orthology Information

Ortholog Group (OrthoMCL): OG6_119330

No human ortholog(s)

Protein Information

Protein Length: 525 | Molecular Weight (kDa): 61.682

UniProt ID(s): Q8IIE7

PDB ID(s): None

Isoelectric Point: 6.77

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000719 Protein kinase domain
InterPro IPR008271 Serine/threonine-protein kinase, active site
InterPro IPR011009 Protein kinase-like domain superfamily
InterPro IPR017441 Protein kinase, ATP binding site
InterPro IPR039046 PDPK1 family
PFam PF00069 Protein kinase domain
Superfamily SSF56112 Protein kinase-like domain superfamily

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 3 21 10 33
disruptive 6 59 33 86
missense 6 54 30 71

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 6 42 18 28
disruptive 18 125 57 130
missense 14 99 51 85

PlasmoDB Total SNPs: 40

Non-coding: 23 | Synonymous: 8 | Nonsynonymous: 9 | Stop Codon: 0

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
34879056 The 3-phosphoinositide-dependent protein kinase 1 is an essential upstreamactivator of protein kinase A in malaria parasites. Hitz E, Wiedemar N, ..., Voss TS 10.1371/journal.pbio.3001483
38277080 Structure-based drug design and molecular dynamics studies of an allosteric modulator targeting the protein-protein interaction site of PDK1 Kailasam Natesan V, Kuppannagounder Pitchaimuthu E 10.1007/s00894-024-05842-2
38278951 D6PK plasma membrane polarity requires a repeated CXX(X)P motif and PDK1-dependent phosphorylation Graf A, Bassukas AEL, ..., Schwechheimer C 10.1038/s41477-023-01615-6
38251029 Ritonavir Has Reproductive Toxicity Depending on Disrupting PI3K/PDK1/AKTSignaling Pathway Jung EJ, Jo JH, ..., Kwon WS 10.3390/toxics12010073
38356720 Disruption of Autophagic Flux and Treatment with the PDPK1 Inhibitor GSK2334470Synergistically Inhibit Renal Cell Carcinoma Pathogenesis Zhou W, Huang J, ..., Tu X 10.7150/jca.92521