Genome location: Pf3D7_08_v3:547,896..551,057(+)
Genome classification: Core
Product Description: hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.5.1.15 (Dihydropteroate synthase);2.7.6.3 (2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005740 | mitochondrial envelope |
| Component | GO:0005634 | nucleus |
| Function | GO:0004156 | dihydropteroate synthase activity |
| Process | GO:0006761 | dihydrofolate biosynthetic process |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0046654 | tetrahydrofolate biosynthetic process |
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 | expressed | 0.41 | 0.83 |
| Trophozoite | expressed | 1.08 | 0.49 |
| Schizont | expressed | 0.09 | 0.95 |
| Gametocyte | not expressed | 0.28 | 0.85 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0810800
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: 0.195 | MFS: -2.767 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1426700)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1426700)
Modification: Mutated | RMgm-5042
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IAU3
"Best" AlphaFill ligand hit: PAB (4-aminobenzoic acid, Local RMSD=0.13) with 6DAY (Global RMSD=3.91)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.5.1.15 | dihydropteroate synthase | KClfolatedapsonWR99210dapsoneTrp-LysPteroateampicillincycloguanilsulfonamidesulfadoxinesulfamoxole... |
| 2.7.6.3 | 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase | AMPKCldapsonePteroatesulfadoxineGuanidine-HClsulfathiazolesulfamethazinesulfamethoxazolesulfadimethoxine8-mercaptoguaninesulfamonomethoxine... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q81VW8 | Dihydropteroate synthase | Bacillus anthracis | OrthoMCL, OrthoMCL BLAST | CHEMBL3827297CHEMBL3828532CHEMBL3828019CHEMBL3828161... |
Protein Length: 706 | Molecular Weight (kDa): 83.374
UniProt ID(s): C0J3L7, C0J3L8, C0J3L9, C0J3M0, C0J3M1, C0J3M2, Q25704, Q25866, Q27738, Q27892, Q8IAU3
PDB ID(s): None
Isoelectric Point: 7.11
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000489 | Pterin-binding domain |
| InterPro | IPR000550 | 7,8-Dihydro-6-hydroxymethylpterin-pyrophosphokinase, HPPK |
| InterPro | IPR006390 | Dihydropteroate synthase |
| InterPro | IPR011005 | Dihydropteroate synthase-like |
| InterPro | IPR035907 | 7,8-Dihydro-6-hydroxymethylpterin-pyrophosphokinase HPPK superfamily |
| PFam | PF00809 | Pterin-binding domain |
| PFam | PF01288 | 7,8-Dihydro-6-hydroxymethylpterin-pyrophosphokinase, HPPK |
| Superfamily | SSF51717 | Dihydropteroate synthase-like |
| Superfamily | SSF55083 | 7,8-Dihydro-6-hydroxymethylpterin-pyrophosphokinase HPPK superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 4 | 7 | 8 |
| disruptive | 11 | 15 | 5 | 33 |
| missense | 11 | 14 | 4 | 25 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 19 | 5 | 28 |
| disruptive | 18 | 39 | 40 | 129 |
| missense | 14 | 26 | 30 | 83 |
PlasmoDB Total SNPs: 123
Non-coding: 82 | Synonymous: 24 | Nonsynonymous: 17 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 9391132 | Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamideresistance in Plasmodium falciparum. | Triglia T, Menting JG, Wilson C, Cowman AF | 10.1073/pnas.94.25.13944 |
| 15279950 | Molecular characterization of bifunctional hydroxymethyldihydropterinpyrophosphokinase-dihydropteroate synthase from Plasmodium falciparum. | Kasekarn W, Sirawaraporn R, ..., Sirawaraporn W | 10.1016/j.molbiopara.2004.04.012 |
| 15642967 | Principal role of dihydropteroate synthase mutations in mediating resistance tosulfadoxine-pyrimethamine in single-drug and combination therapy of uncomplicatedmalaria in Uganda. | Dorsey G, Dokomajilar C, ..., Rosenthal PJ | https://pubmed.ncbi.nlm.nih.gov/15642967/ |
| 20890550 | [Point mutations in dihydrofolate reductase and dihydropteroate synthase genes ofPlasmodium falciparum from three endemic malaria regions in Colombia]. | Galindo JA, Cristiano FA, ..., Guerra AP | https://pubmed.ncbi.nlm.nih.gov/20890550/ |
| 22909027 | Novel quadruple mutations in dihydropteroate synthase genes of Plasmodiumfalciparum in West Bengal, India. | Das S, Chakraborty SP, ..., Roy S | 10.1111/j.1365-3156.2012.03071.x |
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 24321120 | Mutational analysis of Plasmodium falciparum dihydrofolate reductase anddihydropteroate synthase genes in the interior division of Sabah, Malaysia. | Lau TY, Sylvi M, William T | 10.1186/1475-2875-12-445 |
| 25187019 | Two novel mutations of pfdhps K540T and I588F, affectingsulphadoxine-pyrimethamine-resistant response in uncomplicated falciparum malariaat Banjar district, South Kalimantan Province, Indonesia. | Basuki S, Fitriah, ..., Uemura H | 10.1186/1475-2875-13-135 |
| 25311473 | Genetic mutations in Plasmodium falciparum and Plasmodium vivax dihydrofolatereductase (DHFR) and dihydropteroate synthase (DHPS) in Vanuatu and SolomonIslands prior to the introduction of artemisinin combination therapy. | Gresty KJ, Gray KA, ..., Waters NC | 10.1186/1475-2875-13-402 |
| 25943379 | High prevalence of dhfr and dhps molecular markers in Plasmodium falciparum inpregnant women of Nchelenge district, Northern Zambia. | Siame MN, Mharakurwa S, ..., Michelo C | 10.1186/s12936-015-0676-5 |
| 28533179 | Polymorphisms in pfdhfr and pfdhps genes after five years of artemisinincombination therapy (ACT) implementation from urban Kolkata, India. | Chatterjee M, Ganguly S, ..., Maji AK | 10.1016/j.meegid.2017.05.013 |
| 16517168 | Elucidation of sulfadoxine resistance with structural models of the bifunctionalPlasmodium falciparum dihydropterin pyrophosphokinase-dihydropteroate synthase | de Beer TA, Louw AI, Joubert F | 10.1016/j.bmc.2006.02.035 |
| 36124481 | In silico study to predict promiscuous T cell and B cell-epitopes derived fromthe vaccine candidate antigens of Plasmodium vivax binding to MHC class-IIalleles | Khan N, Bin-Mwena MN, ..., Farooq U | 10.4103/0972-9062.335726 |
| 12232841 | Origin and dissemination of Plasmodium falciparum drug-resistance mutations inSouth America | Cortese JF, Caraballo A, Contreras CE, Plowe CV | 10.1086/342946 |
| 15866722 | Purification, properties, and crystallization of Saccharomyces cerevisiaedihydropterin pyrophosphokinase-dihydropteroate synthase | Berglez J, Pilling P, Macreadie I, Fernley RT | 10.1016/j.pep.2005.02.003 |
| 19635897 | Assessment of the origins and spread of putative resistance-conferring mutationsin Plasmodium vivax dihydropteroate synthase | Hawkins VN, Suzuki SM, ..., Sibley CH | https://pubmed.ncbi.nlm.nih.gov/19635897/ |
| 9661026 | Molecular basis of in vivo resistance to sulfadoxine-pyrimethamine in Africanadult patients infected with Plasmodium falciparum malaria parasites | Basco LK, Tahar R, Ringwald P | 10.1128/AAC.42.7.1811 |
| 9178266 | Isolation and molecular characterization of the bifunctionalhydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase gene fromToxoplasma gondii | Pashley TV, Volpe F, ..., Delves CJ | https://pubmed.ncbi.nlm.nih.gov/9178266/ |
| 12165384 | Rapid positive selection of stable integrants following transfection ofPlasmodium falciparum | Wang P, Wang Q, Sims PF, Hyde JE | 10.1016/s0166-6851(02)00105-6 |