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Topic: Dihydrofolate reductase


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In the News (Fri 17 Feb 12)

  
  Dicyclic and Tricyclic Diaminopyrimidine Derivatives as Potent Inhibitors of Cryptosporidium parvum Dihydrofolate ...
Nonclassical 2,4-diamino-8-deazafolate analogues as inhibitors of dihydrofolate reductases from rat liver.
Brominated trimetrexate analogues as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.
2,4-Diamino-6,7-dihydro-5H-cyclopenta[d]pyrimidine analogues of trimethoprim as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase.
aac.asm.org /cgi/content/full/45/12/3293   (5597 words)

  
 Dihydrofolate reductase - Wikipedia, the free encyclopedia
Ribbon diagram of human dihydrofolate reductase in complex with folate (blue).
Dihydrofolate reductase, or DHFR, reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in 1-carbon transfer chemistry.
A variety of drugs act on dihydrofolate reductase, including the antibiotic trimethoprim, the antimalarial drug pyrimethamine, and the chemotherapeutic agents methotrexate and pemetrexed.
en.wikipedia.org /wiki/Dihydrofolate_reductase   (201 words)

  
 Moritella Cold-Active Dihydrofolate Reductase: Are There Natural Limits to Optimization of Catalytic Efficiency at Low ...
Large-scale purification and characterization of dihydrofolate reductase from a methotrexate-resistant strain of Lactobacillus casei.
The dihydrofolate reductase-encoding gene dyrA of the hyperthermophilic bacterium Thermotoga maritima.
Purification and characterization of recombinant Thermotoga maritima dihydrofolate reductase Eur.
jb.asm.org /cgi/content/full/185/18/5519   (4169 words)

  
 Purine and Pyrimidine Metabolism
The enzyme dihydrofolate reductase is responsible for the regeneration of tetrahydrofolate from dihydrofolate.
The compounds aminopterin and methotrexate (amethopterin) are analogs of dihydrofolate.
Methotrexate inhibits the conversion of dihydrofolate to tetrahydrofolate.
www.db.uth.tmc.edu /faculty/alevine/1521_2000/deoxyribo.htm   (1174 words)

  
 Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs.
Pneumocystis carinii was obtained in high yield from the lungs of immunosuppressed rats by rupturing mammalian host cells, washing away the soluble mammalian dihydrofolate reductase, and harvesting intact organisms in association with the mammalian plasma membranes.
carinii dihydrofolate reductase differed from the mammalian enzyme in that the former was slightly inhibited by 150 mM KCl, whereas the latter was stimulated over twofold by 150 mM KCl.
These standard compounds were also tested against dihydrofolate reductase from rat liver to allow an assessment of the selectivity of the drugs.
www.aegis.com /aidsline/1992/jan/M9210253.html   (523 words)

  
 Multiple Mutations Modulate the Function of Dihydrofolate Reductase in Trimethoprim-Resistant Streptococcus pneumoniae ...
Mutations in the dihydrofolate reductase gene of trimethoprim-resistant isolates of Streptococcus pneumoniae.
Saturation mutagenesis at dihydrofolate reductase codons 22 and 31.
A conservative amino acid mutation in the chromosome-encoded dihydrofolate reductase confers trimethoprim resistance in Streptococcus pneumoniae.
aac.asm.org /cgi/content/full/45/4/1104   (2998 words)

  
 Molecular dynamics simulation of Escherichia coli dihydrofolate reductase and its protein fragments: Relative ...
Jennings, P.A., Finn, B.E., Jones, B.E., and Matthews, C.R. A reexamination of the folding mechanism of dihydrofolate reductase from Escherichia coli: Verification and refinement of four-channel model.
Sawaya, M.R. and Kraut, J. Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: Crystallographic evidence.
Touchette, N.A., Perry, K.M., and Matthews, C.R. Folding of dihydrofolate reductase from Escherichia coli.
www.proteinscience.org /cgi/content/full/10/1/135   (5663 words)

  
 CiteULike: Thermal unfolding molecular dynamics simulation of <I>Escherichia coli</I> dihydrofolate ...   (Site not responding. Last check: 2007-10-19)
Temperature-induced unfolding of Escherichia coli dihydrofolate reductase was carried out by using molecular dynamic simulations.
This region, which is made up of part of the N-terminus domain and part of the large domain of the E. coli dihydrofolate reductase, may constitute the nucleation site for protein folding and may be important for the eventual formation of both domains.
Finally, the results of the simulation were found to be consistent with a previous experimental study (Frieden, Proc Natl Acad Sci USA 1990;87:4413-4416) which showed that the folding process of E. coli dihydrofolate reductase involves sequential formation of the substrate-binding sites.
www.citeulike.org /user/choonpeng/article/882436   (499 words)

  
 BioMed Central | Full text | The bifunctional dihydrofolate reductase thymidylate synthase of Tetrahymena ...
Dihydrofolate reductase (DHFR) and thymidylate synthase (TS) are crucial enzymes in DNA synthesis.
DHFR catalyses the production of tetrahydrofolate from dihydrofolate; TS is in charge of transferring a methyl-group from N5, N10-methylene-tetrahydrofolate to dUMP thereby generating dTMP and tetrahydrofolate.
The enzymes dihydrofolate reductase (DHFR) and thymidylate reductase (TS) play a crucial for pyrimidine synthesis, therefore both enzymes have been used as auxotrophic marker-systems in various species by targeted gene disruption.
www.biomedcentral.com /1472-6750/6/21   (3830 words)

  
 Preliminary crystallographic data for Pneumocystis carinii dihydrofolate reductase.
Preliminary crystallographic data for Pneumocystis carinii dihydrofolate reductase.
Dihydrofolate reductase from Pneumocystis carinii has been crystallized in a form suitable for high resolution X-ray diffraction studies.
Recombinant enzyme that had been refolded following solubilization in guanidinium hydrochloride was crystallized as both a ternary complex with the cofactor NADPH and the inhibitor trimethoprim as well as a binary complex with NADPH.
www.aegis.com /aidsline/1993/jul/M9370724.html   (352 words)

  
 CancerQuest : Closer Look : Antimetabolites
Folic acid is a growth factor that provides single carbons to the precursors used to form the nucleotides used in the synthesis of DNA and RNA.
Folate antagonists, also known as antifolates, act by blocking the active site of dihydrofolate reductase (DHFR), an enzyme that reduces folic acid to its active form.
The inhibition of the dihydrofolate reductase keeps the folic acid in an inactive state.
www.cancerquest.org /index.cfm?page=449   (349 words)

  
 QL Protein Secondary Structure Prediction Using Homologues
Dihydrofolate Reductase (E.C.1.5.1.3) Complex With Oxidized Thionicotinamide Adenine Dinucleotide Phosphate And Biopterin pdb1DR4
Dihydrofolate Reductase (E.C.1.5.1.3) With Cys 11 Modified With Methyl Mercury Complex With Nicotinamide Adenine Dinucleotide Phosphate And Biopterin pdb1DR5
Dihydrofolate Reductase (E.C.1.5.1.3) With Cys 11 Covalently Bound To Mercuribenzoate Complex With Nicotinamide Adenine Dinucleotide Phosphate And Biopterin pdb1DR7
abs.cit.nih.gov /ql2/blastprofileinstr.html   (233 words)

  
 Computer modeling of human dihydrofolate reductase ternary complex
Computer modeling with the ESFF forcefield of human dihydrofolate reductase ternary complex with NADPH and piritrexim (PTX) inhibitor.
Dihydrofolate Reductase (DHFR, EC 1.5.1.3) plays an important role in human physiology.
Dihydrofolate reductase (DHFR) is the enzyme catalyzing the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate, with NADPH being a coenzyme in this process [1].
www.phys.uni.torun.pl /~wiesiek/ECCC5/Paper46.html   (5973 words)

  
 DIHYDROFOLATE REDUCTASE AND DIHYDROPTEROATE SYNTHASE GENOTYPES ASSOCIATED WITH IN VITRO RESISTANCE OF PLASMODIUM ...   (Site not responding. Last check: 2007-10-19)
Dihydrofolate reductase (dhfr) genotypes and the half-inhibitory concentration (IC) of P.
falciparum dihydrofolate reductase and dihydropteroate synthase genes and epidemiologic patterns of pyrimethamine/sulfadoxine use and resistance.
Prevalence of dihydrofolate reductase Asp-108 mutation as basis for pyrimethamine resistant falciparum malaria in the Brazilian Amazon.
www.ajtmh.org /cgi/content/full/68/5/586   (2637 words)

  
 The Dihydrofolate Reductase Origin of Replication Does Not Contain Any Nonredundant Genetic Elements Required for ...
The Chinese hamster dihydrofolate reductase replication origin beta is active at multiple ectopic chromosomal locations and requires specific DNA sequence elements for activity.
Initiation of DNA replication in the dihydrofolate reductase locus is confined to the early S period in CHO cells synchronized with the plant amino acid mimosine.
Identification and characterization of a gene that is coamplified with dihydrofolate reductase in a methotrexate-resistant CHO cell line.
mcb.asm.org /cgi/content/full/23/3/804   (8116 words)

  
 Dihydrofolate reductase gene polymorphisms in Pneumocystis carinii f. sp. hominis in Japan -- TAKAHASHI et al. 51 (6): ...
Dihydrofolate reductase gene polymorphisms in Pneumocystis carinii f.
Genetic characterization of the dihydrofolate reductase gene of Pneumocystis jirovecii isolates from Portugal
Dihydropteroate Synthase and Novel Dihydrofolate Reductase Gene Mutations in Strains of Pneumocystis jirovecii from South Africa
jmm.sgmjournals.org /cgi/content/abstract/51/6/510   (290 words)

  
 Directed mutagenesis of dihydrofolate reductase -- Villafranca et al. 222 (4625): 782 -- Science
Three mutations of the enzyme dihydrofolate reductase were constructed by oligonucleotide-directed mutagenesis of the cloned Escherichia coli gene.
The mutations--at residue 27, aspartic acid replaced with asparagine; at residue 39, proline replaced with cysteine; and at residue 95, glycine replaced with alanine--were designed to answer questions about the relations between molecular structure and function that were raised by the x-ray crystal structures.
Role of water in the catalytic cycle of E. coli dihydrofolate reductase.
www.sciencemag.org /cgi/content/abstract/222/4625/782   (459 words)

  
 Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery -- Johnson et al. ...
Common dihydrofolate reductase 19-base pair deletion allele: a novel risk factor for preterm delivery -- Johnson et al.
Dihydrofolate reductase 19–base pair polymorphism in intron 1.
An intron is required for dihydrofolate reductase protein stability.
www.ajcn.org /cgi/content/full/81/3/664   (2903 words)

  
 Ligand Binding Modulates the Mechanical Stability of Dihydrofolate Reductase -- Ainavarapu et al. 89 (5): 3337 -- ...
Dihydrofolate reductase mutant with exceptional resistance to methotrexate but not to trimetrexate.
Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate.
Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence.
www.biophysj.org /cgi/content/full/89/5/3337   (4496 words)

  
 Increased Frequency of Expression of Elevated Dihydrofolate Reductase in T-Cell Versus B-Precursor Acute Lymphoblastic ...
The relationships between dihydrofolate reductase (DHFR) levels or methotrexate membrane transport and acute lymphoblastic leukemia (ALL) immunophenotype were evaluated on 51 T-cell and 44 B-precursor ALL specimens from 90 pediatric ALL patients at diagnosis and relapse, using a fluorescent methotrexate analog (PT430) and flow cytometry assay (Matherly et al, Blood 85:500, 1995).
Hence, ALL patients' lymphoblasts exhibit low-level dihydrofolate reductase (DHFR) gene amplification (2- to 4-fold) and increased DHFR expression at diagnosis and relapse.
Goker E, Waltham M, Kheradpour A, Tippett T, Mazumdar M, Elisseyeff Y, Schnieders B, Steinhertz P, Tan C, Berman E, Bertino JR: Amplification of the dihydrofolate reductase gene is a mechanism of acquired resistance to methotrexate in patients with acute lymphoblastic leukemia and is correlated with p53 gene mutations.
www.bloodjournal.org /cgi/content/full/90/2/578   (6325 words)

  
 Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid - Nature Structural & Molecular Biology
Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid - Nature Structural and Molecular Biology
Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid
Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid&author= Argyrides Argyrou, Matthew W Vetting, Bola Aladegbami and John S Blanchard &contentID=10.1038/nsmb1089&publicationDate=05/01/2006&Vol=13&Issue=5">Rights and permissions
www.nature.com /nsmb/journal/v13/n5/abs/nsmb1089.html   (281 words)

  
 Dihydrofolate reductase antibodies from RDI Divison of Fitzgerald Industries Intl
Dihydrofolate reductase antibodies from RDI Divison of Fitzgerald Industries Intl
Background: Dihydrofolate reductase regenerates tetrahydrofolate from dihydrofolate in the presence of NADPH.
We are not responsible for any patent infringements that might result with the use of or derivation of this product.
www.researchd.com /miscabs/dhfrab.htm   (332 words)

  
 An Intron Is Required for Dihydrofolate Reductase Protein Stability -- Noé et al. 278 (40): 38292 -- Journal of ...
An Intron Is Required for Dihydrofolate Reductase Protein Stability -- Noé et al.
higher in the presence of dihydrofolate reductase intron 1.
of dihydrofolate reductase protein was increased in transfectants
www.jbc.org /cgi/content/abstract/278/40/38292   (386 words)

  
 Moritella Cold-Active Dihydrofolate Reductase: Are There Natural Limits to Optimization of Catalytic Efficiency at Low ...
Moritella Cold-Active Dihydrofolate Reductase: Are There Natural Limits to Optimization of Catalytic Efficiency at Low Temperature?
reductase adaptation to low temperature thus appears to have
Wilquet, V., Van de Casteele, M., Gigot, D., Legrain, C., Glansdorff, N. Dihydropteridine Reductase as an Alternative to Dihydrofolate Reductase for Synthesis of Tetrahydrofolate in Thermus thermophilus.
jb.asm.org /cgi/content/abstract/185/18/5519   (316 words)

  
 ENZYMOLOGY OF CYTOCHROME P450 REDUCTASE
Kinetics studies suggest that this is probably true for the housefly reductase as well.
These redox differences between forms of this enzyme from different species may ultimately be resolved as evolutionary adaptations to different intracellular environments and functions; the protein factors that dictate the different redox potentials of these enzymes have yet to be explored.
Electrostatic interactions play a lesser role with this complex, in part because P450 BM3 and reductase are physically linked on the same polypeptide, rather than separate proteins as in most other systems.
www.uky.edu /Pharmacy/ps/porter/CPR_enzymology.htm   (2558 words)

  
 Discovering rules for the inhibition of E. Coli Dihydrofolate Reductase   (Site not responding. Last check: 2007-10-19)
The data here concerns the classic drug design problem of inhibition of E. Coli Dihydrofolate Reductase by pyrimidines and triazines.
Positive examples are pairs of drugs, the activity of one being known to be higher than the other.
King R.D, Muggleton S., and Sternberg M.J.E. Drug design by machine learning: The use of inductive logic programming to model the structure-activity relationships of trimethoprim analogues binding to dihydrofolate reductase.
www.doc.ic.ac.uk /~shm/e_coli.html   (734 words)

  
 Dihydrofolate Reductase Enzyme Inhibition Assay for Plasma Methotrexate Determination Using a 96-Well Microplate Reader ...
Dihydrofolate Reductase Enzyme Inhibition Assay for Plasma Methotrexate Determination Using a 96-Well Microplate Reader -- Widemann et al.
Dihydrofolate Reductase Enzyme Inhibition Assay for Plasma Methotrexate Determination Using a 96-Well Microplate Reader
In this assay, DHFR catalyzes the reduction of dihydrofolate
www.clinchem.org /cgi/content/full/45/2/223   (2801 words)

  
 PIR-PSD Database [PIR - Protein Information Resource]
View TITLE dihydrofolate reductase (EC 1.5.1.3) / thymidylate synthase (EC 2.1.1.45) - Leishmania major CONTAINS dihydrofolate reductase (EC 1.5.1.3); thymidylate synthase (EC 2.1.1.45) ORGANISM #formal_name Leishmania major DATE 28-Dec-1987 #sequence_revision 28-Dec-1987 #text_change 31-Dec-2004 ACCESSIONS A23403; A24311; A24734; S08691; S14709 REFERENCE A23403 #authors Beverley, S.M.; Ellenberger, T.E.; Cordingley, J.S. #journal Proc.
U.S.A. #title Primary structure of the gene encoding the bifunctional dihydrofolate reductase-thymidylate synthase of Leishmania major.
U.S.A. #title Bifunctional thymidylate synthase-dihydrofolate reductase from Leishmania tropica: sequence homology with the corresponding monofunctional proteins.
pir.georgetown.edu /cgi-bin/nbrfget?uid=RDLNTS   (221 words)

  
 Ultraviolet Resonance Raman Study of Drug Binding in Dihydrofolate Reductase, Gyrase, and Catechol O-Methyltransferase ...
Ultraviolet Resonance Raman Study of Drug Binding in Dihydrofolate Reductase, Gyrase, and Catechol O-Methyltransferase -- Couling et al.
reductase with its inhibitor trimethoprim, gyrase with novobiocin,
Ultraviolet resonance Raman spectroscopic study of the average environment of tyrosine in native and denatured barnase.
www.biophysj.org /cgi/content/full/75/2/1097   (5064 words)

  
 DHFR the MOVIE
The enzyme dihydrofolate reductase (DHFR) catalyzes the reduction of 5,6-dihydrofolate to 5,6,7,8-tetrahydrofolate.
Loop and Domain Movements in the Mechanism of E. Coli Dihydrofolate Reductase: Crystallographic Evidence.
The pathway was first determined by Fierke CA; Johnson KA; Benkovic SJ., Construction and evaluation of the kinetic scheme associated with dihydrofolate reductase from Escherichia coli.
chem-faculty.ucsd.edu /kraut/dhfr.html   (353 words)

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