tetrahydrofolate dehydrogenase

Summary

Summary: An enzyme of the oxidoreductase class that catalyzes the reaction 7,8-dihyrofolate and NADPH to yield 5,6,7,8-tetrahydrofolate and NADPH+, producing reduced folate for amino acid metabolism, purine ring synthesis, and the formation of deoxythymidine monophosphate. Methotrexate and other folic acid antagonists used as chemotherapeutic drugs act by inhibiting this enzyme. (Dorland, 27th ed) EC 1.5.1.3.

Top Publications

  1. pmc A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis
    Gira Bhabha
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 332:234-8. 2011
  2. pmc Drug coverage in treatment of malaria and the consequences for resistance evolution--evidence from the use of sulphadoxine/pyrimethamine
    Allen L Malisa
    Department of Biological Sciences, Faculty of Science, Sokoine University of Agriculture, SUA, PO Box 3038, Morogoro, Tanzania
    Malar J 9:190. 2010
  3. pmc Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies in African Plasmodium falciparum parasite populations
    Sankar Sridaran
    Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mail Stop D 67 Atlanta, GA, 30333, USA
    Malar J 9:247. 2010
  4. ncbi Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence
    M R Sawaya
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0506, USA
    Biochemistry 36:586-603. 1997
  5. ncbi Therapeutic efficacy of chloroquine in Plasmodium vivax from areas with different epidemiological patterns in India and their Pvdhfr gene mutation pattern
    Neena Valecha
    Malaria Research Centre ICMR, 22 Sham Nath Marg, Delhi 110 054, India
    Trans R Soc Trop Med Hyg 100:831-7. 2006
  6. pmc Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates
    M Imwong
    Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Antimicrob Agents Chemother 45:3122-7. 2001
  7. pmc Stepwise acquisition of pyrimethamine resistance in the malaria parasite
    Elena R Lozovsky
    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 106:12025-30. 2009
  8. pmc Network of coupled promoting motions in enzyme catalysis
    Pratul K Agarwal
    Department of Chemistry, 152 Davey Laboratory, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 99:2794-9. 2002
  9. ncbi Dihydrofolate reductase inhibitors as antibacterial agents
    Stephen Hawser
    Arpida Ltd, Dammstrasse 36, 4142 Münchenstein, Switzerland
    Biochem Pharmacol 71:941-8. 2006
  10. pmc Mycobacterium tuberculosis dihydrofolate reductase is not a target relevant to the antitubercular activity of isoniazid
    Feng Wang
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843 2128, USA
    Antimicrob Agents Chemother 54:3776-82. 2010

Research Grants

  1. DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2009
  2. DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIA
    Stephen M Beverley; Fiscal Year: 2010
  3. STRUCTURAL STUDIES ON ENZYMES OF ONE-CARBON METABOLISM
    LAVERNE SCHIRCH; Fiscal Year: 1993
  4. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2007
  5. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2009
  6. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2007
  7. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven H Zeisel; Fiscal Year: 2010
  8. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven H Zeisel; Fiscal Year: 2010
  9. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2009
  10. PURINE AND PTERIDINE METABOLISM
    JESSE RABINOWITZ; Fiscal Year: 1990

Detail Information

Publications228 found, 100 shown here

  1. pmc A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis
    Gira Bhabha
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Science 332:234-8. 2011
    ....
  2. pmc Drug coverage in treatment of malaria and the consequences for resistance evolution--evidence from the use of sulphadoxine/pyrimethamine
    Allen L Malisa
    Department of Biological Sciences, Faculty of Science, Sokoine University of Agriculture, SUA, PO Box 3038, Morogoro, Tanzania
    Malar J 9:190. 2010
    ..These models show that where the basis of resistance is multigenic, the effects of selection can be moderated by high recombination rates, which disrupt the associations between co-selected resistance genes...
  3. pmc Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies in African Plasmodium falciparum parasite populations
    Sankar Sridaran
    Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Mail Stop D 67 Atlanta, GA, 30333, USA
    Malar J 9:247. 2010
    ..This meta-analysis attempts to: 1) summarize genotype frequency data that are critical for molecular surveillance of anti-folate resistance and 2) identify the specific challenges facing the development of future molecular databases...
  4. ncbi Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: crystallographic evidence
    M R Sawaya
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0506, USA
    Biochemistry 36:586-603. 1997
    ..Loop movement, also unobserved in vertebrate DHFR structures, may preferentially weaken NADP+ vs NADPH binding in ecDHFR, an evolutionary adaptation to reduce product inhibition in the NADP+ rich environment of prokaryotes...
  5. ncbi Therapeutic efficacy of chloroquine in Plasmodium vivax from areas with different epidemiological patterns in India and their Pvdhfr gene mutation pattern
    Neena Valecha
    Malaria Research Centre ICMR, 22 Sham Nath Marg, Delhi 110 054, India
    Trans R Soc Trop Med Hyg 100:831-7. 2006
    ..Although P. vivax has been reported to be inherently resistant to sulfonamide and pyrimethamine, Indian isolates exhibited only double mutations in dhfr in vitro...
  6. pmc Association of genetic mutations in Plasmodium vivax dhfr with resistance to sulfadoxine-pyrimethamine: geographical and clinical correlates
    M Imwong
    Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Antimicrob Agents Chemother 45:3122-7. 2001
    ..01). The three mutations at the pvdhfr codons for residues 57, 58, and 117 are associated with high levels of S-P resistance in P. vivax. These mutations presumably arose from selection pressure...
  7. pmc Stepwise acquisition of pyrimethamine resistance in the malaria parasite
    Elena R Lozovsky
    Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 106:12025-30. 2009
    ..Our results also suggest an explanation for why I164L is detected in Southeast Asia and South America, but not at significant frequencies in Africa...
  8. pmc Network of coupled promoting motions in enzyme catalysis
    Pratul K Agarwal
    Department of Chemistry, 152 Davey Laboratory, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 99:2794-9. 2002
    ..This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site...
  9. ncbi Dihydrofolate reductase inhibitors as antibacterial agents
    Stephen Hawser
    Arpida Ltd, Dammstrasse 36, 4142 Münchenstein, Switzerland
    Biochem Pharmacol 71:941-8. 2006
    ..Iclaprim, a recent example of a novel diaminopyrimidine currently in Phase III clinical trials, is also described together with several examples of anti-DHFR antibacterial compounds in pre-clinical development...
  10. pmc Mycobacterium tuberculosis dihydrofolate reductase is not a target relevant to the antitubercular activity of isoniazid
    Feng Wang
    Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843 2128, USA
    Antimicrob Agents Chemother 54:3776-82. 2010
    ..The dfrA overexpression experiments, together with the biochemical and sequencing studies, conclusively demonstrate that DHFR is not a target relevant to the antitubercular activity of INH...
  11. pmc Markers of sulfadoxine-pyrimethamine-resistant Plasmodium falciparum in placenta and circulation of pregnant women
    Frank P Mockenhaupt
    Institute of Tropical Medicine and International Health, Spandauer Damm 130, 14050 Berlin, Germany
    Antimicrob Agents Chemother 51:332-4. 2007
    ..Sulfadoxine-pyrimethamine resistance typing in peripheral blood is reasonably representative of P. falciparum infecting pregnant women...
  12. ncbi Systematic circular permutation of an entire protein reveals essential folding elements
    M Iwakura
    National Institute of Bioscience and Human Technology, 1 1 Higashi, Tsukuba, Ibaraki 305 8566, Japan
    Nat Struct Biol 7:580-5. 2000
    ..However, almost all of the amino acid residues known to be involved in early folding events are located within the folding elements...
  13. pmc miR-192 Regulates dihydrofolate reductase and cellular proliferation through the p53-microRNA circuit
    Bo Song
    Translational Research Laboratory, Department of Pathology, Stony Brook University Medical Center, Stony Brook, New York 11794 8691, USA
    Clin Cancer Res 14:8080-6. 2008
    ..The purpose of this study is to investigate the molecular mechanism of miR-192 in colon cancer...
  14. ncbi Using pharmacophore models to gain insight into structural binding and virtual screening: an application study with CDK2 and human DHFR
    Samuel Toba
    Accelrys Inc, 10188 Telesis Court, Suite 100, San Diego, California 92121, USA
    J Chem Inf Model 46:728-35. 2006
    ..Additionally, automated refinement of the pharmacophore with these excluded volume features provides a more selective model to reduce false positives and a better enrichment rate in virtual screening...
  15. ncbi Repression of the human dihydrofolate reductase gene by a non-coding interfering transcript
    Igor Martianov
    Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
    Nature 445:666-70. 2007
    ....
  16. pmc Pyrosequencing, a high-throughput method for detecting single nucleotide polymorphisms in the dihydrofolate reductase and dihydropteroate synthetase genes of Plasmodium falciparum
    Zhiyong Zhou
    Division of Parasitic Diseases, National Center for Zoonotic, Vector Borne and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Chamblee, Georgia 30341, USA
    J Clin Microbiol 44:3900-10. 2006
    ..Thus, pyrosequencing is a practical alternative method that can be used in a high-throughput format for molecular surveillance of antimalarial-drug resistance...
  17. pmc Carborane clusters in computational drug design: a comparative docking evaluation using AutoDock, FlexX, Glide, and Surflex
    Rohit Tiwari
    Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA
    J Chem Inf Model 49:1581-9. 2009
    ..Binding energies predicted by all four programs were in accordance with experimental data...
  18. ncbi Crystal structure of unliganded Escherichia coli dihydrofolate reductase. Ligand-induced conformational changes and cooperativity in binding
    C Bystroff
    Department of Chemistry, University of California, San Diego, La Jolla 92093
    Biochemistry 30:2227-39. 1991
    ..We explore the idea that the MTX binary complex in some ways resembles the transition-state complex...
  19. pmc Identification of soluble protein fragments by gene fragmentation and genetic selection
    Michael R Dyson
    Department of Biochemistry, University of Cambridge, Downing Site, Cambridge CB2 1QW, UK
    Nucleic Acids Res 36:e51. 2008
    ..This genetic selection method was shown to generate expression clones useful for both structural studies and antibody generation and does not require a priori knowledge of domain architecture...
  20. ncbi Antifolates can have a role in the treatment of Plasmodium vivax
    Vivian N Hawkins
    Department of Genome Sciences, University of Washington, Box 355065, Seattle, WA 98195, USA
    Trends Parasitol 23:213-22. 2007
    ..Other studies have examined the impact of dhps genotype on response to sulfadoxine. These data indicate that, under certain circumstances, SP could be a valuable tool in the fight against P. vivax...
  21. pmc Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin
    Gwladys Bertin
    Institut de recherche pour le developpement IRD, Mère et enfant face aux infections tropicales UMR216, Paris Cedex, France
    Malar J 10:196. 2011
    ..falciparum-infected pregnant women before first and second IPTp administration, and at delivery...
  22. ncbi Intercontinental spread of pyrimethamine-resistant malaria
    Cally Roper
    London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
    Science 305:1124. 2004
    ..The resistance alleles carried by these migrants are now spreading across Africa at an alarming rate, signaling the end of affordable malaria treatment and presenting sub-Saharan Africa with a public health crisis...
  23. ncbi Negative selection using yeast cytosine deaminase/uracil phosphoribosyl transferase in Plasmodium falciparum for targeted gene deletion by double crossover recombination
    Alexander G Maier
    The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
    Mol Biochem Parasitol 150:118-21. 2006
  24. pmc Pyrimethamine and WR99210 exert opposing selection on dihydrofolate reductase from Plasmodium vivax
    Michele D Hastings
    Department of Genome Sciences, University of Washington, Box 357730, Seattle, WA 98195 7730
    Proc Natl Acad Sci U S A 99:13137-41. 2002
    ..If that is the case, this novel class of DHFR inhibitors could provide effective and affordable treatment for chloroquine- and pyrimethamine-resistant vivax and falciparum malaria for many years to come...
  25. ncbi High-efficiency transfection and drug selection of genetically transformed blood stages of the rodent malaria parasite Plasmodium berghei
    Chris J Janse
    Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Nat Protoc 1:346-56. 2006
    ..Genetic modification of P. berghei is widely used to investigate gene function in Plasmodium, and this protocol for high-efficiency transformation will enable the application of large-scale functional genomics approaches...
  26. pmc Selective sweeps and genetic lineages of Plasmodium falciparum drug -resistant alleles in Ghana
    Md Tauqeer Alam
    Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA
    J Infect Dis 203:220-7. 2011
    ..A comprehensive study of the drug-resistance-associated mutations and their genetic lineages will lead to a better understanding of the evolution of antimalarial drug resistance in this region...
  27. pmc Catalysis by dihydrofolate reductase and other enzymes arises from electrostatic preorganization, not conformational motions
    Andrew J Adamczyk
    Department of Chemistry Seeley G Mudd 418, University of Southern California, 3620 McClintock Avenue, Los Angeles, CA 90089, USA
    Proc Natl Acad Sci U S A 108:14115-20. 2011
    ..However, this motion is never the reason for catalysis, but rather simply a reflection of the shape of the reaction potential surface...
  28. pmc Novel point mutations in the dihydrofolate reductase gene of Plasmodium vivax: evidence for sequential selection by drug pressure
    Mallika Imwong
    Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, National Science and Technology Development Agency, Bangkok, Thailand
    Antimicrob Agents Chemother 47:1514-21. 2003
    ..Highly mutated genes carry the S-->T rather than the S-->N mutation at residue 117. Mutations at residues 57 and 61 then occur, followed by a fifth mutation at residue 13...
  29. ncbi Increasing prevalence of wildtypes in the dihydrofolate reductase gene of Plasmodium falciparum in an area with high levels of sulfadoxine/pyrimethamine resistance after introduction of treated bed nets
    Michael Alifrangis
    Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark
    Am J Trop Med Hyg 69:238-43. 2003
    ..The impact of ITNs on the transmission intensity seems not only to affect the overall malaria morbidity, but may even facilitate restoration of susceptibility to antimalarial drugs...
  30. pmc In vitro activity of antifolate and polymorphism in dihydrofolate reductase of Plasmodium falciparum isolates from the Kenyan coast: emergence of parasites with Ile-164-Leu mutation
    Steven M Kiara
    Kenya Medical Research Institute KEMRI Wellcome Trust Collaborative Research Program, P O Box 230, 80108 Kilifi, Kenya
    Antimicrob Agents Chemother 53:3793-8. 2009
    ..We confirmed the presence of this mutation by sequencing. Thus, TMX and MTX are potent against P. falciparum, and quadruple mutants are now emerging in Africa...
  31. ncbi Relating protein motion to catalysis
    Sharon Hammes-Schiffer
    Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Annu Rev Biochem 75:519-41. 2006
    ..This network is comprised of fast thermal motions that are in equilibrium as the reaction progresses along the reaction coordinate and that lead to slower equilibrium conformational changes conducive to the chemical reaction...
  32. pmc Mammalian nuclei become licensed for DNA replication during late telophase
    Daniela S Dimitrova
    Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA
    J Cell Sci 115:51-9. 2002
    ..We conclude that the functional association of Mcm proteins with chromatin (i.e. replication licensing) in CHO cells takes place during telophase, several hours prior to the specification of replication origins at the DHFR locus...
  33. ncbi Sensitivity to antifolates and genetic analysis of Plasmodium vivax isolates from Thailand
    Kanchana Rungsihirunrat
    Faculty of Allied Health Sciences, Thammasat University, Pathumtani, Thailand
    Am J Trop Med Hyg 76:1057-65. 2007
    ..Results suggest that quadruple mutant alleles confer decreased sensitivity to pyrimethamine but retain sensitivity to WR99210...
  34. pmc Chloroquine resistance before and after its withdrawal in Kenya
    Leah Mwai
    Kenya Medical Research Institute Wellcome Trust Collaborative Research Programme, Kilifi, Kenya
    Malar J 8:106. 2009
    ..Changes to those that occurred in the dihydrofolate reductase gene (dhfr) that confers resistance to the replacement drug, pyrimethamine/sulphadoxine were also compared...
  35. pmc Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability and role in angiotensin II uncoupling of endothelial nitric oxide synthase
    Karel Chalupsky
    Section of Cardiology, Department of Medicine, Division of Biological Sciences and Pritzker School of Medicine, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 102:9056-61. 2005
    ..This signaling cascade may represent a universal mechanism underlying eNOS dysfunction under pathophysiological conditions associated with oxidant stress...
  36. ncbi Mutation rates in the dihydrofolate reductase gene of Plasmodium falciparum
    S Paget-McNicol
    The University of Queensland and the Malaria and Arbovirus Unit, Queensland Institute of Medical Research, Australia
    Parasitology 122:497-505. 2001
    ....
  37. pmc Similar trends of pyrimethamine resistance-associated mutations in Plasmodium vivax and P. falciparum
    Mohammad Tauqeer Alam
    Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India
    Antimicrob Agents Chemother 51:857-63. 2007
    ..vivax, suggesting that the drug should be used with caution to minimize the development of cross-species resistance in the field...
  38. ncbi Dihydrofolate reductase mutations in Plasmodium vivax from Indonesia and therapeutic response to sulfadoxine plus pyrimethamine
    Michele D Hastings
    Department of Genome Sciences, School of Medicine, University of Washington, Seattle, WA 98195 7730, USA
    J Infect Dis 189:744-50. 2004
    ..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...
  39. pmc Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors
    Aleem Gangjee
    Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, Pennsylvania 15282, USA
    J Med Chem 51:68-76. 2008
    ..The nonclassical analogues were marginal inhibitors of human TS, but four analogues showed potent T. gondii DHFR inhibition along with >100-fold selectivity compared to human DHFR...
  40. pmc Defining the role of active-site loop fluctuations in dihydrofolate reductase catalysis
    Dan McElheny
    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 102:5032-7. 2005
    ....
  41. pmc Influence of substrate binding on the mechanical stability of mouse dihydrofolate reductase
    J P Junker
    Physik Department E22, Technische Universitat Munchen, D 85748 Garching, Germany
    Biophys J 89:L46-8. 2005
    ..These experiments demonstrate that protein mechanics can be used to probe the substrate binding status of an enzyme...
  42. ncbi Change in mutation patterns of Plasmodium vivax dihydrofolate reductase (Pvdhfr) and dihydropteroate synthase (Pvdhps) in P. vivax isolates from malaria endemic areas of Thailand
    Jiraporn Kuesap
    Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Thammasat University, Pathumthani, Thailand
    Mem Inst Oswaldo Cruz 106:130-3. 2011
    ..vivax isolates in Thailand carry some combination of mutations in Pvdhfr and Pvdhps. Our findings demonstrate that development of new antifolate drugs effective against sulfadoxine-pyrimethamine-resistant P. vivax is required...
  43. pmc Interaction of dihydrofolate reductase with methotrexate: ensemble and single-molecule kinetics
    P T Ravi Rajagopalan
    Department of Chemistry, Pennsylvania State University, 152 Davey Laboratory, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 99:13481-6. 2002
    ..Thus the mechanism of methotrexate binding to DHFR involves multiple steps and protein conformational changes...
  44. pmc Ligand binding modulates the mechanical stability of dihydrofolate reductase
    Sri Rama Koti Ainavarapu
    Department of Biological Sciences, Columbia University, New York, NY, USA
    Biophys J 89:3337-44. 2005
    ..Our observations support the view that the rate-limiting step in protein degradation by adenosine triphosphate-dependent proteases is the mechanical unfolding of the target protein...
  45. pmc Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran
    Sedigheh Zakeri
    Malaria and Vector Research Group MVRG, Biotechnology Research Center, Institut Pasteur of Iran, Pasteur Avenue, PO BOX 1316943551, Tehran, Iran
    Malar J 6:148. 2007
    ..This work was carried out to assess the patterns and prevalence of resistance to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) in Iran...
  46. pmc Tetrahydrobiopterin recycling, a key determinant of endothelial nitric-oxide synthase-dependent signaling pathways in cultured vascular endothelial cells
    Toru Sugiyama
    Cardiovascular and Pulmonary Divisions, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Biol Chem 284:12691-700. 2009
    ....
  47. pmc Deficient BH4 production via de novo and salvage pathways regulates NO responses to cytokines in adult cardiac myocytes
    Irina A Ionova
    Department of Surgery Transplant Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Am J Physiol Heart Circ Physiol 295:H2178-87. 2008
    ....
  48. ncbi Mass spectrometry on segment-specific hydrogen exchange of dihydrofolate reductase
    Tatsuya Yamamoto
    Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi Hiroshima 739 8526
    J Biochem 135:17-24. 2004
    ....
  49. ncbi Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs
    Alyson Auliff
    Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Brisbane, QLD, Australia
    Am J Trop Med Hyg 75:617-21. 2006
    ..Parasites with the S58R/S117N dhfr allelic type showed an MIC level for pyrimethamine and cycloguanil comparable to that previously reported, but were susceptible to WR99210...
  50. pmc Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique
    Sonia Enosse
    Instituto Nacional de Saude, Ministerio de Saude, Maputo, Mozambique
    Malar J 7:115. 2008
    ....
  51. pmc The dihydrofolate reductase origin of replication does not contain any nonredundant genetic elements required for origin activity
    L D Mesner
    Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    Mol Cell Biol 23:804-14. 2003
    ....
  52. pmc Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use
    Alma Brolund
    Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden
    PLoS ONE 5:e9233. 2010
    ..We investigated the distribution of dihydrofolate reductase (dfr)-genes and integrons in Escherichia coli and Klebsiella pneumoniae and the effect of the intervention on this distribution...
  53. ncbi Mitochondrial protein import. Tom40 plays a major role in targeting and translocation of preproteins by forming a specific binding site for the presequence
    D Rapaport
    , , Goethestrasse 33, , Federal Republic of Germany
    J Biol Chem 272:18725-31. 1997
    ..Our study suggests that Tom40 plays an important function in guiding the presequence of a preprotein across the mitochondrial outer membrane. We propose that Tom40 forms a major part of the trans presequence binding site...
  54. ncbi Genetic variations of the dihydrofolate reductase gene of Plasmodium vivax in Mandalay Division, Myanmar
    Byoung Kuk Na
    Department of Molecular Parasitology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440 746, Korea
    Parasitol Res 96:321-5. 2005
    ..Our results suggest that antifolate-resistant P. vivax is becoming widespread in Myanmar, as it also is in the neighboring countries in Southeast Asia. It appears that the drug resistance situation may be worsening in the country...
  55. pmc Plasmodium falciparum drug resistance in Madagascar: facing the spread of unusual pfdhfr and pfmdr-1 haplotypes and the decrease of dihydroartemisinin susceptibility
    Valérie Andriantsoanirina
    Unité de Recherche sur le Paludisme, Institut Pasteur de Madagascar, Antananarivo, Madagascar
    Antimicrob Agents Chemother 53:4588-97. 2009
    ..In the context of the implementation of the new national policy for the fight against malaria, continued surveillance for the detection of P. falciparum resistance in the future is required...
  56. ncbi Plasmodium vivax dihydrofolate reductase point mutations from the Indian subcontinent
    Suminder Kaur
    International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India
    Acta Trop 97:174-80. 2006
    ..Whether these novel mutations are linked to pyrimethamine resistance remains to be established...
  57. ncbi Dispersive initiation of replication in the Chinese hamster rhodopsin locus
    P A Dijkwel
    Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA
    Exp Cell Res 256:150-7. 2000
    ..Thus, the DHFR and rhodopsin origins belong to a class of complex, polydisperse origins that appears to be unique to higher eukaryotic cells...
  58. ncbi Pharmacogenomics of microRNA: a miRSNP towards individualized therapy
    Joseph R Bertino
    Pharmacogenomics 8:1625-7. 2007
  59. pmc Dynamic dysfunction in dihydrofolate reductase results from antifolate drug binding: modulation of dynamics within a structural state
    Randall V Mauldin
    Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Structure 17:386-94. 2009
    ....
  60. ncbi High throughput screening identifies novel inhibitors of Escherichia coli dihydrofolate reductase that are competitive with dihydrofolate
    Michela Zolli-Juran
    McMaster HTS Lab, Department of Biochemistry, McMaster University, Hamilton, ON, Canada L8N 3Z5
    Bioorg Med Chem Lett 13:2493-6. 2003
    ..These novel molecules ranged in potency (K(i)) from 26 nM to 11 microM and may represent fresh starting points for new small molecule therapeutics directed against dihydrofolate reductase...
  61. ncbi Multiplex PCR-RFLP methods for pfcrt, pfmdr1 and pfdhfr mutations in Plasmodium falciparum
    Maria Isabel Veiga
    Center of Molecular and Structural Biomedicine, Universidade do Algarve, Gambelas, Portugal
    Mol Cell Probes 20:100-4. 2006
    ..In this work, we developed a multiplex PCR-RFLP protocols for the diagnosis of these molecular markers, leading to significant decreases in reagent costs, time, number of manipulations and hence human resources...
  62. doi Molecular markers of in vivo Plasmodium vivax resistance to amodiaquine plus sulfadoxine-pyrimethamine: mutations in pvdhfr and pvmdr1
    Jutta Marfurt
    Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, Basel, Switzerland
    J Infect Dis 198:409-17. 2008
    ..However, data on the molecular correlates involved in the development of resistance to 4-aminoquinolines and their association with the in vivo treatment response are scarce...
  63. pmc Low-dose treatment with sulfadoxine-pyrimethamine combinations selects for drug-resistant Plasmodium falciparum strains
    J F Kun
    Department of Parasitology, Institute for Tropical Medicine, University of Tubingen, D 72074 Tubingen, Germany
    Antimicrob Agents Chemother 43:2205-8. 1999
    ..Twenty-four percent had a Ser(436) mutation, and 26% had a Gly(437) mutation. Recrudescent parasites were highly enriched for both Pyr(r) and Sdx(r) strains after treatment (P < 0.001 and P = 0.029, respectively)...
  64. ncbi Analysis of pfcrt, pfmdr1, dhfr, and dhps mutations and drug sensitivities in Plasmodium falciparum isolates from patients in Vietnam before and after treatment with artemisinin
    Thanh Ngo
    Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Melbourne, Australia
    Am J Trop Med Hyg 68:350-6. 2003
    ..High levels of mutation in dhfr and dhps genes, which have previously been associated with Fansidar resistance, also were found, suggesting that this drug would not be useful for malaria control in this part of Vietnam...
  65. ncbi Anticancer antifolates: current status and future directions
    John J McGuire
    Grace Cancer Drug Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
    Curr Pharm Des 9:2593-613. 2003
    ..These new analogs are in various stages of preclinical and clinical development...
  66. ncbi Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli
    R Tahar
    , Centre National de la Recherche Scientifique, 91198, Gif-sur-Yvette, France
    Mol Biochem Parasitol 113:241-9. 2001
    ..The kinetics of enzyme inhibition indicated that point mutations (Ser58Arg and Ser117Asn) are associated with lower affinity between the mutant enzyme and pyrimethamine and cycloguanil, which may be the origin of antifolate resistance...
  67. ncbi Basis for antifolate action and resistance in malaria
    Yongyuth Yuthavong
    National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Rama 6 Road, 10400, Bangkok, Thailand
    Microbes Infect 4:175-82. 2002
    ..New synergistic combinations of drugs targeting DHFR and dihydropteroate synthase may be employed, with new provisions against development of resistance...
  68. pmc Mutations of Pneumocystis jirovecii dihydrofolate reductase associated with failure of prophylaxis
    Aimable Nahimana
    Institute of Microbiology, University Hospital of Lausanne, Rue du Bugnon 48, 1011 Lausanne, Switzerland
    Antimicrob Agents Chemother 48:4301-5. 2004
    ..The results suggest that P. jirovecii populations may evolve under selective pressure from DHFR inhibitors, in particular pyrimethamine, and that DHFR mutations may contribute to P. jirovecii drug resistance...
  69. pmc Origin and dissemination across the Colombian Andes mountain range of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum
    Vladimir Corredor
    Unidad de Parasitologia, Departamento de Salud Publica, Facultad de Medicina, Universidad Nacional de Colombia, Bogota, Colombia
    Antimicrob Agents Chemother 54:3121-5. 2010
    ....
  70. ncbi Incidence of class 1 integrons in multiple antibiotic-resistant Gram-negative copiotrophic bacteria from the River Torsa in India
    Shriparna Mukherjee
    Molecular Microbiology Laboratory, Department of Biotechnology, University of North Bengal, Raja Rammohunpur, Siliguri, West Bengal, India
    Res Microbiol 157:220-6. 2006
    ..TR 90 bearing homology with the Vibrio cholerae dfrA1 gene cassette was characterized. To our knowledge, this is the first report of the incidence and abundance of class 1 integrons in copiotrophic river water bacteria from India...
  71. pmc Different allele prevalence in the dihydrofolate reductase and dihydropteroate synthase genes in Plasmodium vivax populations from China
    Miao Miao
    Department of Entomology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Am J Trop Med Hyg 83:1206-11. 2010
    ..In contrast, except polymorphisms within a repeat region, no resistance-conferring mutations were detected in pvdhps. Our result suggests that P. vivax populations in China may be relatively susceptible to sulfadoxine-pyrimethamine...
  72. pmc Molecular epidemiology of Plasmodium vivax anti-folate resistance in India
    Surendra K Prajapati
    Genetics and Molecular Biology Laboratory, National Institute of Malaria Research NIMR, Sector 8, Dwarka, New Delhi 110077, India
    Malar J 10:102. 2011
    ..This study presents pattern of point mutations in dhfr/dhps genes among Indian sub-continent...
  73. doi Gene amplification and vector engineering to achieve rapid and high-level therapeutic protein production using the Dhfr-based CHO cell selection system
    Jonathan J Cacciatore
    Department of Chemical Engineering, Columbia University, New York, NY 10027, USA
    Biotechnol Adv 28:673-81. 2010
    ..Recent developments that use gene targeting as a method for increasing production are discussed...
  74. ncbi IGF-I alleviates diabetes-induced RhoA activation, eNOS uncoupling, and myocardial dysfunction
    Jun Ren
    School of Pharmacy, University of Wyoming, Laramie, WY 82071, USA
    Am J Physiol Regul Integr Comp Physiol 294:R793-802. 2008
    ..These results revealed that IGF-I benefits diabetic hearts via Rho inhibition and antagonism of diabetes-induced decrease in pAkt, eNOS uncoupling, and K+ channel expression...
  75. ncbi Geographical distribution of amino acid mutations in Plasmodium vivax DHFR and DHPS from malaria endemic areas of Thailand
    Kanchana Rungsihirunrat
    Faculty of Allied Health Sciences, Thammasat University, Pathumtani, Thailand
    Am J Trop Med Hyg 78:462-7. 2008
    ..Novel mutations that have not been identified previously at codon 512 of pvdhps (K512M, K512E, K512T) were also found...
  76. doi Characterization of a novel trimethoprim resistance gene, dfrA28, in class 1 integron of an oligotrophic Acinetobacter johnsonii strain, MB52, isolated from River Mahananda, India
    Arvind Kumar
    Microbial Biotechnology Laboratory, Department of Biotechnology, University of North Bengal, Siliguri, India
    Microb Drug Resist 16:29-37. 2010
    ..4% amino acid identity with DfrA1. A gene for streptomycin resistance, aminoglycoside adenyl transferase aadA1, was located downstream of dfrA28. Phylogenetic analysis of MB52 identified it as a strain of Acinetobacter johnsonii...
  77. ncbi Application of destabilizing sequences on selection marker for improved recombinant protein productivity in CHO-DG44
    Say Kong Ng
    Singapore MIT Alliance, National University of Singapore, 4 Engineering Drive 3, E4 04 10, Singapore 117576, Singapore
    Metab Eng 9:304-16. 2007
    ..A high specific IFNgamma productivity of 1.05pg/cell/day was also attained by the amplified cell pool with both ARE and MODC PEST...
  78. pmc A winding road to origin discovery
    Joyce L Hamlin
    Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, USA
    Chromosome Res 18:45-61. 2010
    ..After all, in the words of George Santayana, "Those who do not learn from history are doomed to repeat it."..
  79. pmc Molecular characterization of antifolates resistance-associated genes, (dhfr and dhps) in Plasmodium vivax isolates from the Middle East
    Sedigheh Zakeri
    Malaria and Vector Research Group MVRG, Biotechnology Research Center, Institut Pasteur of Iran, Tehran, Iran
    Malar J 8:20. 2009
    ..vivax infections are often exposed to sulphadoxine-pyrimethamine (SP). In the present study, the frequency distribution of mutations associated to SP resistance was investigated in pvdhfr and pvdhps genes from field isolates...
  80. ncbi Dihydrofolate reductase: x-ray structure of the binary complex with methotrexate
    D A Matthews
    Science 197:452-5. 1977
    ....
  81. pmc Coordinated effects of distal mutations on environmentally coupled tunneling in dihydrofolate reductase
    Lin Wang
    Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 103:15753-8. 2006
    ..This observation is in accordance with the notion that these remote residues are part of a dynamic network that is coupled to the catalyzed chemistry...
  82. pmc Prevalence of pfmdr1, pfcrt, pfdhfr and pfdhps mutations associated with drug resistance, in Luanda, Angola
    Paula Figueiredo
    UEI Malária Centro de Malária e Doenças Tropicais IHMT Universidade Nova de Lisboa, Lisbon, Portugal
    Malar J 7:236. 2008
    ..Loss of SP sensitivity is, however, progressing rapidly in Africa and, in this study, were investigated a number of molecular markers associated to CQ and S/P...
  83. pmc 2,4-Diamino-5-methyl-6-substituted arylthio-furo[2,3-d]pyrimidines as novel classical and nonclassical antifolates as potential dual thymidylate synthase and dihydrofolate reductase inhibitors
    Aleem Gangjee
    Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, United States
    Bioorg Med Chem 18:953-61. 2010
    ..This study shows that the furo[2,3-d]pyrimidine scaffold is conducive to dual human DHFR-TS inhibitory activity and to high potency and selectivity for pathogen DHFR...
  84. pmc Plasmodium falciparum: a novel method for analyzing haplotypes in mixed infections
    Laura K Certain
    University of Washington, Department of Genome Sciences, Seattle, WA 98195, USA
    Exp Parasitol 115:233-41. 2007
    ..Because each plasmid contains only one insert and each yeast colony contains only one plasmid, the individual strains are now separate. We analyzed mixtures of 3D7, K1, and Dd2 DNA and correctly identified a haplotype in each case...
  85. pmc Competitive facilitation of drug-resistant Plasmodium falciparum malaria parasites in pregnant women who receive preventive treatment
    W E Harrington
    Seattle Biomedical Research Institute, 307 Westlake Avenue N, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 106:9027-32. 2009
    ..Use of partially effective anti-malarial agents for IPTp may exacerbate malaria infections in the setting of widespread drug resistance...
  86. pmc Mutations in the antifolate-resistance-associated genes dihydrofolate reductase and dihydropteroate synthase in Plasmodium vivax isolates from malaria-endemic countries
    Feng Lu
    Department of Parasitology, Kangwon National University College of Medicine, Chuncheon, Republic of Korea
    Am J Trop Med Hyg 83:474-9. 2010
    ..These findings suggests that the prevalence of mutations in pvdhfr and pvdhps in P. vivax isolates from different malaria-endemic countries is associated with selection pressure imposed by sulfadoxine-pyrimethamine...
  87. ncbi Molecular characterization of dihydrofolate reductase in relation to antifolate resistance in Plasmodium vivax
    Ubolsree Leartsakulpanich
    National Centre for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Rama 6 Road, 10400, Bangkok, Thailand
    Mol Biochem Parasitol 119:63-73. 2002
    ..Data on kinetic parameters and inhibitory constant suggest that the wild-type P. vivax is susceptible to antimalarial antifolates and that point mutations in the DHFR domain of P. vivax are responsible for antifolate resistance...
  88. doi Molecular surveillance of drug-resistant Plasmodium vivax using pvdhfr, pvdhps and pvmdr1 markers in Nouakchott, Mauritania
    Khadijetou Mint Lekweiry
    Laboratoire de Biotechnologies, Faculte des Sciences et Techniques, Université de Nouakchott, Mauritania
    J Antimicrob Chemother 67:367-74. 2012
    ..vivax isolates in Nouakchott, the capital city of Mauritania, and to establish a baseline for molecular surveillance of drug-resistant P. vivax in the country...
  89. pmc Transgenic Plasmodium parasites stably expressing Plasmodium vivax dihydrofolate reductase-thymidylate synthase as in vitro and in vivo models for antifolate screening
    Voravuth Somsak
    Protein Ligand Engineering and Molecular Biology Laboratory, National Center for Genetic Engineering and Biotechnology BIOTEC, National Science and Technology Development Agency, Thailand Science Park, Pathumthani 12120, Thailand
    Malar J 10:291. 2011
    ..vivax parasites...
  90. ncbi Cancer research: from folate antagonism to molecular targets
    Joseph R Bertino
    Department of Molecular Therapeutics, The Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA
    Best Pract Res Clin Haematol 22:577-82. 2009
    ..MTX remains a potent and widely used agent...
  91. pmc Dynamics and dissipation in enzyme catalysis
    Nicholas Boekelheide
    Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Mail Code 127 72, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 108:16159-63. 2011
    ..This work finds a minimal role for nonlocal vibrational dynamics in enzyme catalysis, and it supports a model in which nanometer-scale protein fluctuations statistically modulate--or gate--the barrier for the intrinsic reaction...
  92. ncbi Increased gametocytemia after treatment: an early parasitological indicator of emerging sulfadoxine-pyrimethamine resistance in falciparum malaria
    Karen I Barnes
    Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa
    J Infect Dis 197:1605-13. 2008
    ..Although malaria treatment aims primarily to eliminate the asexual blood stages that cause illness, reducing the carriage of gametocytes is critical for limiting malaria transmission and the spread of resistance...
  93. pmc Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors
    Xin Zhang
    Division of Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA
    Bioorg Med Chem 19:3585-94. 2011
    ....
  94. doi Insights into antifolate activity of phytochemicals against Pseudomonas aeruginosa
    Premkumar Jayaraman
    Biomedical Engineering Research Centre, Nanyang Technological University, Singapore
    J Drug Target 19:179-88. 2011
    ..Taken together, the above findings provide novel insights to mode of interactions of these phytochemicals with antibiotics and may have significance as prospective leads in the development of antipseudomonal drug developments...
  95. pmc Nuclear magnetic resonance study of the role of M42 in the solution dynamics of Escherichia coli dihydrofolate reductase
    Randall V Mauldin
    Department of Biochemistry and Biophysics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599 7568, USA
    Biochemistry 49:1606-15. 2010
    ..These data show that the M42W mutation alters the dynamics of DHFR and are consistent with theoretical analysis that suggests this mutation disrupts motion that promotes catalysis...
  96. doi Mechanism of inhibition of wt-dihydrofolate reductase from E. coli by tea epigallocatechin-gallate
    Michele Spina
    Department of Molecular, Cellular and Animal Biology, University of Camerino, Via Gentile III da Varano, 62032, Camerino MC, Italy
    Proteins 72:240-51. 2008
    ..Collectively, our data have confirmed the selectivity of antifolate compounds with respect to the different source of enzyme (bacterial or mammalian DHFR) and the possible role of tea catechins as chemopreventive agents...
  97. doi Novel mutations in the antifolate drug resistance marker genes among Plasmodium vivax isolates exhibiting severe manifestations
    Shilpi Garg
    Department of Biological Sciences, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India
    Exp Parasitol 132:410-6. 2012
    ..However, the presence of novel mutations in the PvDHPS gene indicate a degree of polymorphism of this molecule which is in contrast to available published information...
  98. ncbi Interloop contacts modulate ligand cycling during catalysis by Escherichia coli dihydrofolate reductase
    G P Miller
    Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Biochemistry 40:867-75. 2001
    ..These findings suggest that the role of the interloop interaction between the betaG-betaH loop and the Met20 loop is to modulate ligand off rates allowing for proper cycling through the preferred kinetic pathway...
  99. pmc Use of molecular beacons to detect an antifolate resistance-associated mutation in Plasmodium falciparum
    R Durand
    Centre National de Reference pour la Chimiosensibilite du Paludisme, Université Paris V et Assistance Publique Hôpitaux de Paris, Hopital Bichat Claude Bernard, Laboratoire de Parasitologie, Paris, France
    Antimicrob Agents Chemother 44:3461-4. 2000
    ..One hundred African clinical isolates were tested by the new method in comparison with the PCR-restriction fragment length polymorphism method. This new molecular technique appears to be a promising tool for epidemiological studies...
  100. ncbi Effect of N-terminal truncation of Plasmodium falciparum dihydrofolate reductase on dihydrofolate reductase and thymidylate synthase activity
    Jantanee Wattanarangsan
    National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathumthani 12120, Thailand
    Mol Biochem Parasitol 126:97-102. 2003
  101. pmc Molecular determination of point mutation haplotypes in the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum in three districts of northern Tanzania
    Richard J Pearce
    Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, United Kingdom
    Antimicrob Agents Chemother 47:1347-54. 2003
    ..The triple-dhfr/double-dhps genotype is present in all three regions with frequencies ranging between 30 and 63%, indicating that treatment failure rates are likely to be high...

Research Grants81

  1. DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIA
    Stephen Beverley; Fiscal Year: 2009
    ..10-CHO-THF) in Leishmania metabolism and biology, and to study the enzyme 5,10-methylene tetrahydrofolate dehydrogenase/cyclohydrolase (DHCH1) primarily responsible for its synthesis...
  2. DRUG RESISTANCE AND PTERIDINE METABOLISM IN LEISHMANIA
    Stephen M Beverley; Fiscal Year: 2010
    ..10-CHO-THF) in Leishmania metabolism and biology, and to study the enzyme 5,10-methylene tetrahydrofolate dehydrogenase/cyclohydrolase (DHCH1) primarily responsible for its synthesis...
  3. STRUCTURAL STUDIES ON ENZYMES OF ONE-CARBON METABOLISM
    LAVERNE SCHIRCH; Fiscal Year: 1993
    ..2: Determine the structure and mechanism of 5,10-methenyl tetrahydrofolate synthetase and 10-formyl tetrahydrofolate dehydrogenase. These two enzymes are believed to play critical roles in regulating one-carbon metabolism, yet little ..
  4. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2007
    ..04) and premenopausal women with a common snp in methylene tetrahydrofolate dehydrogenase (MTHFD1-1958A) had an OR of >85 (p=.0001) for developing signs of choline deficiency...
  5. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2009
    ..04) and premenopausal women with a common snp in methylene tetrahydrofolate dehydrogenase (MTHFD1-1958A) had an OR of >85 (p=.0001) for developing signs of choline deficiency...
  6. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2007
    ..04) and premenopausal women with a common snp in methylene tetrahydrofolate dehydrogenase (MTHFD1-1958A) had an OR of >85 (p=.0001) for developing signs of choline deficiency...
  7. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven H Zeisel; Fiscal Year: 2010
    ..04) and premenopausal women with a common snp in methylene tetrahydrofolate dehydrogenase (MTHFD1-1958A) had an OR of >85 (p=.0001) for developing signs of choline deficiency...
  8. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven H Zeisel; Fiscal Year: 2010
    ..04) and premenopausal women with a common snp in methylene tetrahydrofolate dehydrogenase (MTHFD1-1958A) had an OR of >85 (p=.0001) for developing signs of choline deficiency...
  9. HUMAN REQUIREMENTS FOR THE NUTRIENT CHOLINE
    Steven Zeisel; Fiscal Year: 2009
    ..04) and premenopausal women with a common snp in methylene tetrahydrofolate dehydrogenase (MTHFD1-1958A) had an OR of >85 (p=.0001) for developing signs of choline deficiency...
  10. PURINE AND PTERIDINE METABOLISM
    JESSE RABINOWITZ; Fiscal Year: 1990
    ..corresponding monofunctional bacterial enzymes, 10-formyl- tetrahydrofolate synthetase, 5,10-methylene-tetrahydrofolate dehydrogenase, and 5,10-methenyl-tetrahydrofolate cyclohydrolase, will be examined...
  11. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2006
    ....
  12. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2006
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  13. Novel Single, Dual and Multitargeted Inhibitors of RTKs
    Aleem Gangjee; Fiscal Year: 2007
    ..abstract_text> ..
  14. Novel Single, Dual and Multitargeted Inhibitors of RTKs
    Aleem Gangjee; Fiscal Year: 2006
    ..abstract_text> ..
  15. Third Generation Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2001
    ..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
  16. NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORS
    Aleem Gangjee; Fiscal Year: 2004
    ....
  17. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2008
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. ..
  18. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2010
    ....
  19. Single Agents with Designed Combination Chemotherapy Potential
    Aleem Gangjee; Fiscal Year: 2010
    ..abstract_text> ..
  20. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2010
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. ..
  21. Single Agents with Designed Combination Chemotherapy Potential
    Aleem Gangjee; Fiscal Year: 2009
    ..abstract_text> ..
  22. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2009
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  23. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2009
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. ..
  24. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2008
    ....
  25. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2008
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  26. Third Generation Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2003
    ..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
  27. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2007
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. [unreadable] [unreadable]..
  28. NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORS
    Aleem Gangjee; Fiscal Year: 2002
    ....
  29. NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORS
    Aleem Gangjee; Fiscal Year: 2001
    ....
  30. Third Generation Antiopportunistic Agents
    Aleem Gangjee; Fiscal Year: 2002
    ..Screening against tuberculosis (NIAID) and tumor cells in culture (NCI) is also proposed. ..
  31. Novel Single, Dual and Multitargeted Inhibitors of RTKs
    Aleem Gangjee; Fiscal Year: 2003
    ....
  32. STRUCTURE BASED ANALOGS AS ANTIOPPORTUNISTIC AGENTS
    Aleem Gangjee; Fiscal Year: 2001
    ..The analogues synthesized will also be submitted for screening against tuberculosis (NIAID) parasitic diseases (WHO) and tumor cells in culture (NCI). ..
  33. STRUCTURE BASED ANALOGS AS ANTIOPPORTUNISTIC AGENTS
    Aleem Gangjee; Fiscal Year: 2000
    ..The analogues synthesized will also be submitted for screening against tuberculosis (NIAID) parasitic diseases (WHO) and tumor cells in culture (NCI). ..
  34. NOVEL NONINDUCIBLE THYMIDYLATE SYNTHASE INHIBITORS
    Aleem Gangjee; Fiscal Year: 2003
    ....
  35. Novel, P. jirovecii Specific Antipneumocystis Agents
    Aleem Gangjee; Fiscal Year: 2007
    ..These agents could be used alone or in combination to treat PCP thus providing novel agents against a new target. ..
  36. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2007
    ....
  37. Antitumor Antimitotics That Reverse Tumor Resistance
    Aleem Gangjee; Fiscal Year: 2006
    ..The study will also further define the mechanism of action of the novel series and could afford agents for clinical use. [unreadable] [unreadable]..
  38. Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
    Aleem Gangjee; Fiscal Year: 2009
    ....
  39. STRUCTURE BASED ANALOGS AS ANTIOPPORTUNISTIC AGENTS
    Aleem Gangjee; Fiscal Year: 1999
    ..The analogues synthesized will also be submitted for screening against tuberculosis (NIAID) parasitic diseases (WHO) and tumor cells in culture (NCI). ..
  40. STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGS
    Vivian Cody; Fiscal Year: 2001
    ..Dr. Sherry Queener, Indiana University, will measure inhibitory activity of selected antifolates. ..
  41. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2008
    ..These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilitiesin the structure-based correlations to help design novel pjDHFRinhibitors. ..
  42. STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGS
    Vivian Cody; Fiscal Year: 2000
    ..Dr. Sherry Queener, Indiana University, will supply samples of pcDHFR and measure the pc activity of new antifolates. ..
  43. STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGS
    Vivian Cody; Fiscal Year: 2003
    ..Dr. Sherry Queener, Indiana University, will measure inhibitory activity of selected antifolates. ..
  44. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2009
    ..These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilitiesin the structure-based correlations to help design novel pjDHFRinhibitors. ..
  45. STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGS
    Vivian Cody; Fiscal Year: 2004
    ..Dr. Sherry Queener, Indiana University, will measure inhibitory activity of selected antifolates. ..
  46. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2009
    ..These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilitiesin the structure-based correlations to help design novel pjDHFRinhibitors. ..
  47. STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGS
    Vivian Cody; Fiscal Year: 1999
    ..Dr. Sherry Queener, Indiana University, will supply samples of pcDHFR and measure the pc activity of new antifolates. ..
  48. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2006
    ..Mutagenesis studies will be carried out to test these possibilities in the structure-based correlations to help design novel pjDHFR inhibitors. [unreadable] [unreadable]..
  49. STRUCTURAL STUDIES OF AIDS RESPONSIVE DRUGS
    Vivian Cody; Fiscal Year: 2002
    ..Dr. Sherry Queener, Indiana University, will measure inhibitory activity of selected antifolates. ..
  50. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2007
    ..Mutagenesis studies will be carried out to test these possibilities in the structure-based correlations to help design novel pjDHFR inhibitors. [unreadable] [unreadable]..
  51. Structural Studies of AIDS-Responsive Drugs
    Vivian Cody; Fiscal Year: 2010
    ..These results will help guide the design of species selective inhibitors. Mutagenesis studies will be carried out to test these possibilitiesin the structure-based correlations to help design novel pjDHFRinhibitors. ..
  52. NEW APPROACHES TO ANTIFOLATE CHEMOTHERAPY
    Andre Rosowsky; Fiscal Year: 1980
    ..Once this has been done, appropriate pre-clinical studies will be performed and an IND application for a Phase I evaluation in man will be filed. ..
  53. LIPOPHILIC ANTIFOLATES AND AIDS OPPORTUNISTIC INFECTIONS
    Andre Rosowsky; Fiscal Year: 1992
    ....
  54. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2009
    ....
  55. Simulation of Protein and Hydride Transfer in Enzymes
    Sharon Hammes Schiffer; Fiscal Year: 2005
    ..In mammals, lipoxygenases are medically relevant, in that they mediate processes such as asthma, atherosclerosis, psoriasis, inflammatory diseases, and cancer growth. ..
  56. Simulation of Protein and Hydride Transfer in Enzymes
    Sharon Hammes Schiffer; Fiscal Year: 2003
    ..In mammals, lipoxygenases are medically relevant, in that they mediate processes such as asthma, atherosclerosis, psoriasis, inflammatory diseases, and cancer growth. ..
  57. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2002
    ..The elucidation of the detailed mechanisms of LADH and GO will enhance the understanding of and guide the optimization of their biochemical and biomedical properties. ..
  58. Simulation of Protein and Hydride Transfer in Enzymes
    Sharon Hammes Schiffer; Fiscal Year: 2006
    ..In mammals, lipoxygenases are medically relevant, in that they mediate processes such as asthma, atherosclerosis, psoriasis, inflammatory diseases, and cancer growth. ..
  59. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2007
    ....
  60. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2001
    ..The elucidation of the detailed mechanisms of LADH and GO will enhance the understanding of and guide the optimization of their biochemical and biomedical properties. ..
  61. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2008
    ....
  62. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2000
    ..The elucidation of the detailed mechanisms of LADH and GO will enhance the understanding of and guide the optimization of their biochemical and biomedical properties. ..
  63. SIMULATION OF PROTON AND HYDRIDE TRANSFER IN ENZYMES
    Sharon Hammes Schiffer; Fiscal Year: 2009
    ....
  64. Simulation of Protein and Hydride Transfer in Enzymes
    Sharon Hammes Schiffer; Fiscal Year: 2004
    ..In mammals, lipoxygenases are medically relevant, in that they mediate processes such as asthma, atherosclerosis, psoriasis, inflammatory diseases, and cancer growth. ..
  65. UW Northern Rockies Regional INBRE
    Jun Ren; Fiscal Year: 2008
    ..abstract_text> ..
  66. IGF-1, Oxidative Stress and Cardiovascular Aging
    Jun Ren; Fiscal Year: 2002
    ..Our long-term goal is to establish the causal link among IGF-1 deficiency, enhanced oxidative damage and ventricular dysfunction in the progression of cardiovascular aging so that hormonal or antioxidant therapy can be optimized...
  67. Folic Acid Enhances Repair Mechanism in the Adult CNS
    Bermans Iskandar; Fiscal Year: 2009
    ....
  68. Kinetic Intermediates in Folding of Histone Dimers
    LISA GLOSS; Fiscal Year: 2007
    ..When these processes go awry because of misregulation of nucleosome function, assembly and dynamics, disease states result, particularly cancer. [unreadable] [unreadable] [unreadable]..
  69. Single Molecule Studies of Enzyme Catalysis
    Gordon Hammes; Fiscal Year: 2002
    ..These experiments are directed at understanding better how enzymes catalyze physiological reactions. A better understanding of enzyme mechanisms is essential for understanding the physiology of disease and the development of new drugs. ..
  70. Strategies for mapping origins in mammalian genomes
    JOYCE HAMLIN; Fiscal Year: 2004
    ..The predictive value of the computational approach will be tested on the remaining 20 percent of validated origins (the test set). ..