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Plasmodium falciparum hexose transporter

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Target not currently curated in GtoImmuPdb

Malaria Pharmacology Ligand  Target has curated data in GtoMPdb

Target id: 3069

Nomenclature: Plasmodium falciparum hexose transporter

Abbreviated Name: PfHT1

Family: Transporters (Plasmodium spp.)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 504 HT1 hexose transporter
Gene and Protein Information Comments
PfHT1 is the single annotated hexose transporter in the Plasmodium genome. It is a member of the SLC2 family of hexose and sugar alcohol transporters but is highly divergent in sequence from all human orthologs with GLUT1, the most closely related human ortholog, sharing <30% amino acid identity with PfHT1 [3-4].
Previous and Unofficial Names Click here for help
HT1 | Pf3D7_02_v3:204,784..207,425(-) | hexose transporter 1 | HT | PF02_0044 | PFB0210c
Database Links Click here for help
Alphafold Q7KWJ5 (Pf3D7)
PlasmoDB PF3D7_0204700 (Pf3D7)
UniProtKB Q7KWJ5 (Pf3D7)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Plasmodium falciparum hexose transporter PfHT1 bound with C3361
PDB Id:  6M2L
Resolution:  3.7Å
Species:  Plasmodium falciparum
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Plasmodium falciparum hexose transporter PfHT1 bound with glucose
PDB Id:  6M20
Resolution:  2.6Å
Species:  Plasmodium falciparum
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  The molecular basis for sugar import in malaria parasites
PDB Id:  6RW3
Resolution:  3.65Å
Species:  Plasmodium falciparum
References:  5
Whole Organism Assay Data Linked to This Target
Key to terms and symbols Click column headers to sort
Ligand Sp. Assay description Type Action Value Parameter Reference
HTI-1 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
✖
 Parasite growth inhibition assay - - 6.4 pEC50 3
⤷ pEC50 6.4 (EC50 3.77x10-7 M) SYBR Green I assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
HTI-1 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfDd2

Plasmodium falciparum Dd2

P. falciparum strain Dd2 (PfDd2) is a clone derived from PfW2, following continuous culture in mefloquine. PfW2 was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy.
PfDd2 can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, pyrimethamine and mefloquine.
✖
 Parasite growth inhibition assay - - 6.4 pEC50 3
⤷ pEC50 6.4 (EC50 3.98x10-7 M) SYBR Green I assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
TCMDC-125163 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfK1

Plasmodium falciparum K1

P. falciparum strain K1 (PfK1) was isolated in Kanchanaburi, Thailand in 1979.
PfK1 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be a multidrug-resistant strain.
✖
 Parasite growth inhibition assay - - 6.0 pEC50 4
⤷ pEC50 6.0 (EC50 9.7x10-7 M) SYBR Green I assay [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
TCMDC-125163 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
✖
 Parasite growth inhibition assay - - 5.8 pEC50 4
⤷ pEC50 5.8 (EC50 1.4x10-6 M) SYBR Green I assay [4]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
The P. falciparum hexose transporter (PfHT1) mediates glucose uptake, an essential process because the intraerythrocytic stages of the parasite's lifecycle are dependent upon host glucose for energy [6].
PfHT1 shows promise as a target for antimalarial drug development with a focus on identifying compounds that inhibit the parasite permease without impairing function of human SLC2 transporters. It is a target "under consideration" in the Malaria Drug Accelerator (MalDA) portfolio [1].
Studies using a structure-guided design approach have identified small molecules that selectively target PfHT1 and simultaneously bind both orthosteric and allosteric pockets of the transporter [2-3]. These PfHT1 inhibitors lack many of the drug-like properties required for clinical advancement but will help inform future drug discovery efforts.

References

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1. Forte B, Ottilie S, Plater A, Campo B, Dechering KJ, Gamo FJ, Goldberg DE, Istvan ES, Lee M, Lukens AK et al.. (2021) Prioritization of Molecular Targets for Antimalarial Drug Discovery. ACS Infect Dis, 7 (10): 2764-2776. [PMID:34523908]

2. Huang J, Yuan Y, Zhao N, Pu D, Tang Q, Zhang S, Luo S, Yang X, Wang N, Xiao Y et al.. (2021) Orthosteric-allosteric dual inhibitors of PfHT1 as selective antimalarial agents. Proc Natl Acad Sci U S A, 118 (3). [PMID:33402433]

3. Jiang X, Yuan Y, Huang J, Zhang S, Luo S, Wang N, Pu D, Zhao N, Tang Q, Hirata K et al.. (2020) Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum. Cell, 183 (1): 258-268.e12. [PMID:32860739]

4. Ortiz D, Guiguemde WA, Johnson A, Elya C, Anderson J, Clark J, Connelly M, Yang L, Min J, Sato Y et al.. (2015) Identification of Selective Inhibitors of the Plasmodium falciparum Hexose Transporter PfHT by Screening Focused Libraries of Anti-Malarial Compounds. PLoS ONE, 10 (4): e0123598. [PMID:25894322]

5. Qureshi AA, Suades A, Matsuoka R, Brock J, McComas SE, Nji E, Orellana L, Claesson M, Delemotte L, Drew D. (2020) The molecular basis for sugar import in malaria parasites. Nature, 578 (7794): 321-325. [PMID:31996846]

6. Woodrow CJ, Penny JI, Krishna S. (1999) Intraerythrocytic Plasmodium falciparum expresses a high affinity facilitative hexose transporter. J Biol Chem, 274 (11): 7272-7. [PMID:10066789]

How to cite this page

Transporters (Plasmodium spp.): Plasmodium falciparum hexose transporter. Last modified on 11/12/2021. Accessed on 16/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3069.