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Showing 1 to 20 of 31 for “"Dihydrofolate Reductase"”.
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Computational Studies on R67 Dihydrofolate Reductase: An Investigation Into Its Unique Binding Patterns
<p>R67 dihydrofolate reductase (R67 DHFR) is a plasmid encoded enzyme which catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) using NADPH as a cofactor. R67 DHFR is a homo-tetramer and D2 symmetric. It contains only one active site, which spans the central channel of the …
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Primary structure and expression studies of the dihydrofolate reductase gene (DFRI) of Saccharomyces cerevisiae
… DNA fragment thought previously to contain the dihydrofolate reductase gene (DFR1) of Saccharomyces cerevisiae by genetic criteria was determined. This DNA fragment of 1784' basepairs contains a large open reading frame from position 800 to 1432, which encodes a enzyme with a predicted molecular …
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Synthesis and Molecular Modeling Studies of Bicyclic Inhibitors of Dihydrofolate Reductase, Receptor Tyrosine Kinases and Tubulin
… et al. against the following targets:</p><p> 1. Dihydrofolate reductase: human, P. carinii, P. jirovecii (pjDHFR) and T. gondii (tgDHFR)</p><p> 2. Thymidylate synthase: human (hTS) and T. gondii (tgTS)</p><p> 3. Receptor tyrosine kinases: VEGFR2, EGFR and PDGFR-β</p><p> 4. Colchicine binding site …
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Study of the Cryptosporidium parvum DHFR-TS in the model system Saccharomyces cerevisiae
… for compounds effective against the C. parvum dihydrofolate reductase (DHFR) enzyme. The DHFR enzyme is essential and an effective drug target in other organisms. The yeast screening method has identified several compounds that are effective inhibitors of the C. parvum DHFR but also inhibit the …
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Validation and Application of a Novel Target-Based Whole-Cell Screen to Identify Antifungal Compounds
… albicans and validated this approach using dihydrofolate reductase. However, our approach, which we have termed target abundance-based fitness screening (TAFiS), should be applicable to an extensive array of molecular targets and in any genetically tractable microbe.</p> <p>While the folate …
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Asymmetric reduction using enzymes and Chiral chemical reagents
… on a preparative scale. In the first case dihydrofolate reductase was used to catalyse the conversion of 7,8-dihydrofolic acid into (6S)- 5,6,7, B-tetrahydrofolic acid. The required coenzyme,NADPH, was recycled 1100 fold in situ using coupled enzyme techniques. The reaction was quantitative …
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Characterisation of trimethoprim resistance transposons and their gene products
… resemblence between the trimethoprim resistant dihydrofolate reductase (DHFR) of Escherichia coli J62(RP4::Tn4135) and that of the type I plasmid enzyme, encoded by RP4::Tn7_. Despite the differences in transposon size, this marked similarity between the two DHFRs suggests a similar evolutionary …
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Synthesis of Bicyclic Thieno[2,3-d]Pyrimidines, Tricyclic Thieno[2,3-d]Pyrimidines and Thieno[3,2-d]Pyrimidines as Classical and Nonclassical Antifolates
… and discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. As a part of this study, thirty-five …
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The mechanistic basis of susceptibility and resistance to the antitubercular drug para-aminosalicylic acid
… folate biosynthetic pathway, to hydroxy-dihydrofolate. The folate biosynthesis pathway is an essential metabolic pathway used maintain the production of DNA, RNA, and proteins. Results showed that hydroxy-dihydrofolate acted as a potent inhibitor for dihydrofolate reductase and confirm …
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Synthesis of furo[2,3-d]pyrimidines, thieno[2,3- d]pyrimidines, pyrrolo[2,3-d]pyrimidines as classical and nonclassical antifolates, receptor tyrosine kinase (RTK) inhibitors and antimitotic agents
… has been discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. Classical antifolates, in most …
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Target Based Design and Synthesis of Fused Pyrimidines in the Potential Treatment of Cancer and Opportunistic Infection
… as (a) selective <em>Pneumocystis jirovecii</em> dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential treatment of cancer; and (c) substrates for tumor-targeted …
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Protein Dynamics and its Correlation to Protein Activity and Stability
… examine the current paradigm using the enzyme: dihydrofolate reductase as a model. As inferred by neutron spectroscopy, the binding of MTX influences the dynamical behavior of DHFR. Macromolecular dynamics such as the resilience: lt;kgt; (i.e. structural rigidity) was found to be increased and, …
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The Structural Distribution of Epistasis in a Pair of Essential Metabolic Enzymes
… in the bacterial folate metabolic pathway, Dihydrofolate Reductase (DHFR) and Thymidylate Synthase (TYMS). To achieve this goal, I used deep mutational scanning assays on DHFR in the context of varying activities of TYMS. The result is a rigorous dataset with epistasis measurements over the …
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Toward therapeutic nanoassemblies: the design and modeling of protein-protein interactions.
… of a bis-methotrexate (bis-MTX) induced E. coli dihydrofolate reductase (DHFR) dimer over a dynamic range of 1.5 kcal/mol. Furthermore, we have employed single-molecule fluorescence assays to demonstrate the stabilization of a heterodimeric DHFR dimer, yielding 4-fold selectivity for the …
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Synthesis and translation of novel gram-negative antibacterial agents
… inhibitors), and 2,4-diaminopyrimidines (dihydrofolate reductase inhibitors). The acrylamide-linked naphthyridinones campaign has been successful, culminating in the discovery of fabimycin which has broad spectrum activity versus problematic clinical pathogens while sparing healthy gut …
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Screening and Characterization of Antimicrobial Compounds and Material against Vibrio cholerae
… function similar to trimethoprim, targeting the dihydrofolate reductase of V. cholerae. This compound has the potential to be developed as a trimethoprim replacement with a minimum inhibitory concentration lower by 14-fold. Next, the antibacterial property of a newly synthesized cellulose aerogel …
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Metabolism and Handling of Folates in the Mammal Especially Man
… Oral folate metabolism in the presence of a dihydrofolate reductase inhibitor (methotrexate) administered orally 24 hour before the test was studied. No evidence could be found for a build up of dihydrofolic acid.
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Studies in the Folate Metabolism of Rats
… methotrexate is in addition to the inhibition of dihydrofolate reductase. In view of this, the effects of 6-mercaptopurine, a classical purine inhibitor, on folate metabolism were studied. In addition to the characterization of urinary metabolites, an effort was made to identify the nature of …
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Noncanonical recognition and degradation of a stable soluble protein by AAA protease FtsH
… for FtsH to successfully bind and unfold E. coli dihydrofolate reductase (DHFR), a stable protein which was previously found to resist FtsH degradation. Strikingly, I find that detergent-solubilized FtsH can degrade DHFR in vitro with or without an appended degron. I then show that FtsH …
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