Molecule Information

General Information of the Molecule (ID: Mol02087)

• Name: Bifunctional dihydrofolate reductase-thymidylate synthase (PFDHFR) ,Plasmodium falciparum
• Synonyms: dhfr
• Molecule Type: Protein
• Gene Name: Pfdhfr
• Sequence:
  DIYAICACCKVESKNEGKKNEVFNNYTFRGLGNKGVLPWKCNSLDMKYFRAVTTYVNESK
  YEKLKYKRCKYLNKETVDNVNDMPNSKKLQNVVVMGRTNWESIPKKFKPLSNRINVILSR
  TLKKEDFDEDVYIINKVEDLIVLLGKLNYYKCFIIGGSVVYQEFLEKKLIKKIYFTRINS
  TYEC
• Function: Bifunctional enzyme. Involved in de novo dTMP biosynthesis. Key enzyme in folate metabolism. Catalyzes an essential reaction for de novo glycine and purine synthesis, DNA precursor synthesis, and for the conversion of dUMP to dTMP.
• Uniprot ID: A0A0U2XGD2_PLAFA

Kingdom: N.A.
Phylum: Apicomplexa
Class: Aconoidasida
Order: 5819
Family: Plasmodiidae
Genus: Plasmodium
Species: Plasmodium falciparum

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Proguanil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Falciparum malaria [1]

• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Resistant Drug: Proguanil
• Molecule Alteration: Missense mutation; p.N51I
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

Disease Class: Falciparum malaria [1]

• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Resistant Drug: Proguanil
• Molecule Alteration: Missense mutation; p.N51I
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

Disease Class: Falciparum malaria [1]

• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Resistant Drug: Proguanil
• Molecule Alteration: Missense mutation; p.C59R
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

Disease Class: Falciparum malaria [1]

• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Resistant Drug: Proguanil
• Molecule Alteration: Missense mutation; p.S108N
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

References

• Ref 1: Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile .Am J Trop Med Hyg. 2021 Mar 29;104(5):1811-1813. doi: 10.4269/ajtmh.20-1095. 10.4269/ajtmh.20-1095