Dihydrofolate Reductase from Pyrimethamine-resistant Plasmodium berghei

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Dihydrofolate reductase from pyrimethamine-resistant Plasmodium berghei.

An investigation of the Hz-folate reductases from pyrimethamine-sensitive (Pb/WLTM) and -resistant (Pb/ WLTM/50-63) strains of Plasmodium berghei has revealed that the specific activity of the enzyme from the resistant strain is IO-fold higher than that of the sensitive strain. Since turnover numbers (based on amethopterin binding) are equivalent, the increase in specific activity must be due t...

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Rare, highly pyrimethamine-resistant alleles of the Plasmodium falciparum dihydrofolate reductase gene from 5 African sites.

In eastern and southern Africa, there has been a rapid increase in the prevalence of alleles with mutations in the Plasmodium falciparum dihydrofolate reductase gene (dhfr) associated with increased risk of clinical failure of sulfadoxine-pyrimethamine (S/P). Molecular methods for surveillance of these mutations are now widespread, but the usual analysis detects only the most prevalent allele i...

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Pyrimethamine-resistant dihydrofolate reductase enzymes of Plasmodium falciparum are not enzymatically compromised in vitro.

Plasmodium falciparum, the protozoan that causes the most lethal form of human malaria, has been controlled principally by two safe, affordable drugs, chloroquine and sulfadoxine-pyrimethamine (SP). Studies in the laboratory and in the field have demonstrated that resistance to SP depends on non-synonymous point mutations in the dihydrofolate reductase (DHFR), and dihydropteroate synthase (DHPS...

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Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine.

BACKGROUND The target enzyme of pyrimethamine is dihydrofolate reductase (DHFR), but little is known about allelic variants of dhfr in Plasmodium vivax populations. Still less is known about associations between specific alleles and the failure of sulfadoxine/pyrimethamine (S/P) to clear the erythrocytic stages of P. vivax in vivo. METHODS We studied P. vivax dhfr mutations in 24 patients who...

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Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase from Plasmodium vivax.

Plasmodium vivax is a major public health problem in Asia and South and Central America where it is most prevalent. Until very recently, the parasite has been effectively treated with chloroquine, but resistance to this drug has now been reported in several areas. Affordable alternative treatments for vivax malaria are urgently needed. Pyrimethamine-sulfadoxine is an inhibitor of dihydrofolate ...

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ژورنال

عنوان ژورنال: Journal of Biological Chemistry

سال: 1970

ISSN: 0021-9258

DOI: 10.1016/s0021-9258(18)63342-3