About Gene List

PF3D7_0104400 (LytB)

Genome location: Pf3D7_01_v3:201,354..204,250(+)

Genome classification: Core

Function and Localization

Product Description: 4-hydroxy-3-methylbut-2-enyl diphosphate reductase

SignalP Peptide: N/A

# Transmembrane Domains: 1

EC Numbers: 1.17.1.2 (Transferred entry: 1.17.7.4);1.17.7.4 (4-hydroxy-3-methylbut-2-enyl diphosphate reductase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020011 apicoplast
Function GO:0051745 4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase activity
Process GO:0019288 isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway

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 expressed 0.15 0.92
Trophozoite expressed 0.48 0.72
Schizont expressed 0.26 0.82
Gametocyte expressed 0.87 0.54

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0104400

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: Mutable in CDS

MIS: 0.993 | MFS: -2.596 | #Insertions: 1

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I295

"Best" AlphaFill ligand hit: POP (pyrophosphate 2-, Local RMSD=0.52) with 3F7T (Global RMSD=2.27)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
1.17.1.2 4-hydroxy-3-methylbut-2-enyl diphosphate reductase No BRENDA inhibitors
1.17.7.4 4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase BPH-293ImidazolBPH-1029pyridine-N-oxidepropargyl alcoholN-methylpyridiniumpropargyl diphosphatebut-3-ynyl diphosphatepyridin-2-ylmethyl diphosphatepyridin-3-ylmethyl diphosphate2-(pyridin-3-yl)ethyl diphosphatepyridin-4-ylmethyl trihydrogen diphosphate...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
O67625 4-hydroxy-3-methylbut-2-enyl diphosphate reductase OrthoMCL, OrthoMCL BLAST IspH inhibitor, 9PYRIDIN-3-YL-ETHYL-DIPHOSPHATEBUT-3-YNYL DIPHOSPHATEPYRIDIN-3-YL-ETHYL-DIPHOSPHATE...
Q9HVM7 4-hydroxy-3-methylbut-2-enyl diphosphate reductase OrthoMCL, OrthoMCL BLAST IspH inhibitor, 8
P62623 4-hydroxy-3-methylbut-2-enyl diphosphate reductase OrthoMCL, OrthoMCL BLAST IspH inhibitor, 9

Orthology Information

Ortholog Group (OrthoMCL): OG6_105777

No human ortholog(s)

Protein Information

Protein Length: 535 | Molecular Weight (kDa): 62.47

UniProt ID(s): Q8I295, Q9BJX6

PDB ID(s): None

Isoelectric Point: 9.79

Protein Domain Annotations:

Source Family ID Description
InterPro IPR003451 4-hydroxy-3-methylbut-2-enyl diphosphate reductase
PFam PF02401 4-hydroxy-3-methylbut-2-enyl diphosphate reductase
Superfamily N/A N/A

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 4 28 10 35
disruptive 5 34 27 62
missense 5 33 24 50

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 9 50 25 44
disruptive 21 94 42 100
missense 13 75 33 66

PlasmoDB Total SNPs: 160

Non-coding: 136 | Synonymous: 13 | Nonsynonymous: 11 | 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
16289098 Reconstitution of an apicoplast-localised electron transfer pathway involved inthe isoprenoid biosynthesis of Plasmodium falciparum. Rohrich RC, Englert N, ..., Wiesner J 10.1016/j.febslet.2005.10.037
21690250 Apicoplast isoprenoid precursor synthesis and the molecular basis of fosmidomycinresistance in Toxoplasma gondii. Nair SC, Brooks CF, ..., Striepen B 10.1084/jem.20110039
24188825 Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase fromPlasmodium falciparum. Rekittke I, Olkhova E, ..., Ermler U 10.1016/j.febslet.2013.10.029
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
30191613 Exploration and validation of diphosphate-based Plasmodium LytB inhibitors using computational approaches Bhuyan R, Seal A 10.1002/jmr.2762
31756006 Methylerythritol Phosphate Pathway: Enzymatic Evidence for a Rotation in theLytB/IspH-Catalyzed Reaction Chaignon P, Petit BE, ..., Seemann M 10.1002/chem.201904676
28862365 Further Insight into Crystal Structures of Escherichia coli IspH/LytB in Complex with Two Potent Inhibitors of the MEP Pathway: A Starting Point for RationalDesign of New Antimicrobials Borel F, Barbier E, ..., Seemann M 10.1002/cbic.201700363
28933084 [Cloning and bioinformatics analysis of 1-hydroxy-2-methyl-2-(E)-butenyl4-diphosphate reductase_PcHDR1_gene in Phlegmarirus carinatus] Zhang ZL, Lv HZ, ..., Luo HM 10.4268/cjcmm20162214