Resistance to sulfadoxine-pyrimethamine (SP) in Plasmodium falciparum malaria parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes, and these mutations have spread resistance worldwide. SP, used for several years in Senegal, has been recommended for intermittent preventive treatment for malaria in pregnancy (IPTp) and has been wi...

Type I signal-anchor sequences mediate translocation of the N-terminal domain (N-domain) across the endoplasmic reticulum (ER) membrane. To examine the translocation in detail, dihydrofolate reductase (DHFR) was fused to the N-terminus of synaptotagmin II as a long N-domain. Translocation was arrested by the DHFR ligand methotrexate, which stabilizes the folding of the DHFR domain, and resumed ...

Background: This study investigated the prevalence of antimalarial drug resistance markers in P. falciparum isolates, involving the detection of mutations at the mdr1-86, which associates with amodiaquine resistance, and dhfr mutations associated with SP resistances. Methods: The dot-blot/probe hybridization was used to determine multidrug resistance (mdr1-86) and assess the correlation of Amod...

Mutations create the genetic diversity on which selective pressures can act, yet also create structural instability in proteins. How, then, is it possible for organisms to ameliorate mutation-induced perturbations of protein stability while maintaining biological fitness and gaining a selective advantage? Here we used site-specific chromosomal mutagenesis to introduce a selected set of mostly d...

Problem statement: Dihydrofolate Reductase (DHFR) and Thymidylate Synthase (TS) exist as bifunctional enzymes coded into unique polypeptide chain in protozoans. Bifunctional DHFRTS is associated with an increase in the enzymatic activity by channeling the substrate between the active sites. In some bacteria, DHFR and TS genes are neighbors in the genome, whereas in others, they are located mill...

The antifolate drugs sulfadoxine and pyrimethamine are commonly used to treat Plasmodium falciparum malaria. However, they can also affect the Plasmodium vivax parasite if it coexists with P. falciparum, as both species have common drug targets. Resistance to the antifolate drugs arises due to point mutations in the target enzymes of the respective parasite. To assess the cross-species impact o...

Dihydrofolate reductase (DHFR) is an important enzyme for de novo synthesis of nucleotides in Plasmodium falciparum and it is essential for cell proliferation. DHFR is a well known antimalarial target for drugs like cycloguanil and pyrimethamine which target its inhibition for their pharmacological actions. However, the clinical efficacies of these antimalarial drugs have been compromising due ...

Pathogenic Escherichia coli, one of the primary causes of urinary tract infections, has shown significant resistance to the most popular antibiotic, trimethoprim (TMP), which inhibits dihydrofolate reductase (DHFR). The resistance is modulated by single point mutations of DHFR. The impact of two clinically relevant mutations, P21L and W30R, on the activity of DHFR was evaluated via measurement ...

The Chinese hamster lung cell line DC-3F contains two polymorphic di hydro l'oliile reducÃ-ase (DHFR) alÃ-elesthai are defined by an Asp-Asn amino acid sequence difference al posilion 95 in Ihe prolein. Previously, we reported thai Ihe anlifolale-resistant subline DC-3F/A3 overexpressed a I cu.* -»Phe mulanl of Ihe Asp95 (21k) alÃ-eleand that this was Ihe basis of its resistance to melholrexal...

OBJECTIVE Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis...