Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We isolated a panel of 20 DNA probes that hybridize specifically to chromosome No. 4 of Plasmodium falciparum and used them to construct a restriction map of chromosome No. 4 in the FCR3 strain. These probes were partially sequenced and had an insert size range of 70-310 bp (average 160 bp) and a GC content range of 19-53% (average 35%). Three probes were identical to previously described P. falciparum sequences. Two probes were homologous to an 18-bp repetitive sequence in a previously cloned P. falciparum gene but were not homologous to other parts of the gene. One probe sequence is a homologue of the heat shock protein, DnaJ. The location of these probes and four previously cloned probes on chromosome No. 4 were determined by using eight restriction enzymes that recognize 6-bp sites containing only G or C and 10 restriction enzymes that recognize 6-bp sites containing four G or C and two A or T. The locations of the probes were well distributed along the chromosome. Three probes were located at two sites and two probes were found at at least four sites on chromosome No. 4. Maps of chromosome No. 4 of the FCR3 strain, and three laboratory-selected, pyrimethamine-resistant derivative strains were constructed. Two of the strains, FCR3-D81 and FCR3-D85, each had two polymorphic forms of chromosome No. 4. Each of those polymorphic chromosomes had a duplicated part of the center of the chromosome making the cell diploid for the genetic material in that region. Those chromosomes also had an amplification and probable intrachromosomal translocation of a 50-kb fragment of chromosome No. 4. One strain derived from FCR3-D7, FCR3-D7-1 contained 20 copies of a tandemly amplified fragment carrying the dihydrofolate reductase-thymidylate synthase gene and an amplification of an unrelated part of the chromosome.
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PMID:Establishing a physical map of chromosome No. 4 of Plasmodium falciparum. 796 62

Mdj1p, a novel member of the DnaJ family, is a heat shock protein that is associated with the inner membrane of mitochondria of Saccharomyces cerevisiae. Disruption of the MDJ1 gene resulted in a petite phenotype, loss of mitochondrial DNA, and inviability at 37 degrees C. Import of precursor proteins was not affected by a lack of Mdj1p, but folding of newly imported proteins was markedly impaired. The efficiency of refolding of a tester protein, dihydrofolate reductase, was significantly reduced in mitochondria lacking Mdj1p after incubation at elevated temperature. We conclude that Mdj1p is an important mitochondrial chaperone that participates in the folding of newly imported proteins and in the protection of proteins against heat denaturation and aggregation.
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PMID:Mdj1p, a novel chaperone of the DnaJ family, is involved in mitochondrial biogenesis and protein folding. 816 33

The folding of proteins into their native structures is known to depend on molecular chaperones. However, other ligands or cofactors which still require characterisation are also likely to influence protein folding. The intention of this study was to reveal how the folding of an enzyme, Escherichia coli dihydrofolate reductase, was affected by a substrate ligand, i.e. dihydrofolate. The enzyme was synthesised by coupled transcription/translation in a bacterial cell-free system. Correct folding of the protein into its native structure was measured by its enzymatic activity. Synthesis of dihydrofolate reductase was found to be inhibited, at the level of translation, by dihydrofolate. The syntheses of other proteins were also inhibited by this compound and the reasons for this inhibition could not be determined. Most notably, the specific activity of the dihydrofolate reductase formed in the presence of the substrate dihydrofolate was increased and this effect was specific for dihydrofolate reductase since it was not observed with other proteins synthesised in the same system. The increase in dihydrofolate reductase specific activity could not be attributed to mere thermal stabilisation of the fully folded enzyme by dihydrofolate. The effects of dihydrofolate on dihydrofolate reductase synthesis and activity were similar to those of the molecular chaperone DnaJ which is known to promote the folding of newly synthesised proteins. It is suggested that dihydrofolate may interact with the newly synthesised dihydrofolate reductase polypeptide chain and promote its productive folding.
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PMID:Dihydrofolate influences the activity of Escherichia coli dihydrofolate reductase synthesised de novo. 1071 30

Trimethoprim (TMP), an inhibitor of dihydrofolate reductase, decreases the level of tetrahydrofolate supplying one-carbon units for biosynthesis of nucleotides, proteins, and panthotenate. We have demonstrated for the first time that one of the effects of the TMP action in E. coli cells is protein aggregation and induction of heat shock proteins (Hsps). TMP caused induction of DnaK, DnaJ, GroEL, ClpB, and IbpA/B Hsps. Among these Hsps, IbpA/B were most efficiently induced by TMP and coaggregated with the insoluble proteins. Upon folate stress, deletion of the delta ibpA/B operon resulted in increased protein aggregation but did not influence cell viability.
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PMID:Trimethoprim induces heat shock proteins and protein aggregation in E. coli cells. 1462 8