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