Genome location: Pf3D7_14_v3:2,750,164..2,752,514(+)
Genome classification: Core
Product Description: 1-deoxy-D-xylulose 5-phosphate reductoisomerase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 1.1.1.267 (1-deoxy-D-xylulose-5-phosphate reductoisomerase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Function | GO:0030604 | 1-deoxy-D-xylulose-5-phosphate reductoisomerase activity |
| Function | GO:0070402 | NADPH binding |
| Function | GO:0030145 | manganese ion binding |
| Process | GO:0051484 | isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway involved in terpenoid biosynthetic process |
| 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 | 0.18 | 0.87 |
| Schizont | expressed | 0.03 | 0.97 |
| Gametocyte | possibly expressed | 0.05 | 0.97 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1467300
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.149 | MFS: -2.918 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1330600)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKG4
"Best" AlphaFill ligand hit: FOM (fosmidomycin, Local RMSD=0.16) with 3AU9 (Global RMSD=0.63)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.1.1.267 | 1-deoxy-D-xylulose-5-phosphate reductoisomerase | EDTANADP+ThymoleugenolcarveolcatechinlinaloolFR900098quercetinbaicaleincarvacrolFR-900098... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q8IKG4 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplastic | HOGENOM, OMA, OrthoDB, OrthoMCL BLAST | CHEMBL4215008Fosmidomycin SodiumCHEMBL4202817CHEMBL4207168... | |
| Q9XFS9 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, chloroplastic | HOGENOM, OMA, OrthoMCL, OrthoMCL BLAST | fosmidomycin | |
| P9WNS1 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase | Mycobacterium tuberculosis | OMA, OrthoMCL, OrthoMCL BLAST | CHEMBL2164256CHEMBL3341763CHEMBL3342262CHEMBL258981... |
| P45568 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase | Escherichia coli | OMA, OrthoMCL, OrthoMCL BLAST | Bi-ligand, 3Bi-ligand, 4(1E,1'E)-O,O'-(Ethane-1,2-diyl)bis[2,4,5-trihydroxybenzaldehyde oxime] (5)(E)-2,4,5-Trihydroxybenzaldehyde oxime (7)... |
| Q55663 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase | Synechocystis sp. | OMA, OrthoMCL, OrthoMCL BLAST | fosmidomycin |
| A0QVH7 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase | Mycobacterium smegmatis | OMA, OrthoMCL BLAST | fosmidomycinfosmidomycinFR-900098CHEMBL1161784... |
Protein Length: 488 | Molecular Weight (kDa): 55.757
UniProt ID(s): A0A144A2T4, A5HNU7, A5HNU8, A5HNU9, A5HNV0, A5HNV1, Q8IKG4
PDB ID(s): 4Y67, 4Y6P, 4Y6R, 4Y6S, 5JAZ, 5JBI, 5JC1, 5JMP, 5JMW, 5JNL, 5JO0
Isoelectric Point: 8.79
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR003821 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase |
| InterPro | IPR013512 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, N-terminal |
| InterPro | IPR013644 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, C-terminal |
| InterPro | IPR026877 | DXP reductoisomerase C-terminal domain |
| InterPro | IPR036169 | DXP reductoisomerase, C-terminal domain superfamily |
| InterPro | IPR036291 | NAD(P)-binding domain superfamily |
| PFam | PF02670 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, N-terminal |
| PFam | PF08436 | 1-deoxy-D-xylulose 5-phosphate reductoisomerase, C-terminal |
| PFam | PF13288 | DXP reductoisomerase C-terminal domain |
| Superfamily | SSF51735 | NAD(P)-binding domain superfamily |
| Superfamily | SSF55347 | DXP reductoisomerase, C-terminal domain superfamily |
| Superfamily | SSF69055 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 27 | 15 | 17 |
| disruptive | 7 | 54 | 38 | 78 |
| missense | 7 | 54 | 38 | 72 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 49 | 14 | 26 |
| disruptive | 16 | 109 | 50 | 100 |
| missense | 16 | 101 | 47 | 81 |
PlasmoDB Total SNPs: 102
Non-coding: 78 | Synonymous: 17 | Nonsynonymous: 7 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 20018214 | Functional genetic analysis of the Plasmodium falciparum deoxyxylulose5-phosphate reductoisomerase gene. | Odom AR, Van Voorhis WC | 10.1016/j.molbiopara.2009.12.001 |
| 20214634 | The malarial drug target Plasmodium falciparum 1-deoxy-D-xylulose-5-phosphatereductoisomerase (PfDXR): development of a 3-D model for identification of novel,structural and functional features and for inhibitor screening. | Goble JL, Adendorff MR, ..., Blatch GL | 10.2174/092986610789909548 |
| 21573242 | Fosmidomycin uptake into Plasmodium and Babesia-infected erythrocytes isfacilitated by parasite-induced new permeability pathways. | Baumeister S, Wiesner J, ..., Seeber F | 10.1371/journal.pone.0019334 |
| 22355528 | Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodiumfalciparum. | Umeda T, Tanaka N, ..., Nakamura KT | 10.1038/srep00009 |
| 24032981 | IspC as target for antiinfective drug discovery: synthesis, enantiomericseparation, and structural biology of fosmidomycin thia isosters. | Kunfermann A, Lienau C, ..., Kurz T | 10.1021/jm4012559 |
| 27650666 | In silico identification of promiscuous scaffolds as potential inhibitors of1-deoxy-d-xylulose 5-phosphate reductoisomerase for treatment of Falciparummalaria. | Wadood A, Ghufran M, ..., Rashid U | 10.1080/13880209.2016.1225778 |
| 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 |