BibSonomyburst/user/nutribiochemBibSonomy RSS feed for /user/nutribiochem2012-02-16T08:28:14+01:00http://www.bibsonomy.org/bibtex/2652326609f5ca067f5f6782a7f884d25/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span class="authorEditorList"><a href="/author/Becker">Katja Becker</a> </span><em>Spiegel der Forschung</em> <em>24(1):42-47</em> (<em>2007</em>)Tue Oct 14 16:07:18 CEST 2008Spiegel der Forschung142-47Molekulare Maschinen und Alterung � der humane Redoxstoffwechsel242007IFZ imported http://www.bibsonomy.org/bibtex/2ac10738f97d6701e59384add4eee6266/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span class="authorEditorList"><a href="/author/Becker">K. Becker</a>, and <a href="/author/Schirmer">H. R. Schirmer</a> </span><em>Biospektrum</em> <em>02(07):138-141</em> (<em>2007</em>)Tue Oct 14 16:07:18 CEST 2008Biospektrum07138-141Antioxidative Enzyme des Malariaerregers als Targets von Bonaria-Medikamenten022007IFZ imported http://www.bibsonomy.org/bibtex/288be58900ce4b5c3072293d9fbc91bf8/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Animals Base_Sequence Blotting DNA_Primers IFZ Life_Cycle_Stages Messenger Peroxidases Plasmodium_berghei RNA Rats Reverse_Transcriptase_Polymerase_Chain_Reaction Western <span class="authorEditorList"><a href="/author/Buchholz">Kathrin Buchholz</a>, <a href="/author/Rahlfs">Stefan Rahlfs</a>, <a href="/author/Schirmer">Heiner R. Schirmer</a>, <a href="/author/Becker">Katja Becker</a>, and <a href="/author/Matuschewski">Kai Matuschewski</a> </span><em>PLoS ONE</em> <em>3(6):e2474-e2474</em> (<em>2008</em>)Tue Oct 14 16:07:18 CEST 2008PLoS ONE6e2474-e2474Depletion of Plasmodium berghei plasmoredoxin reveals a non-essential role for life cycle progression of the malaria parasite32008Animals Base_Sequence Blotting DNA_Primers IFZ Life_Cycle_Stages Messenger Peroxidases Plasmodium_berghei RNA Rats Reverse_Transcriptase_Polymerase_Chain_Reaction Western Proliferation of the pathogenic Plasmodium asexual blood stages in host erythrocytes requires an exquisite capacity to protect the malaria parasite against oxidative stress. This function is achieved by a complex antioxidant defence system composed of redox-active proteins and low MW antioxidants. Here, we disrupted the P. berghei plasmoredoxin gene that encodes a parasite-specific 22 kDa member of the thioredoxin superfamily. The successful generation of plasmoredoxin knockout mutants in the rodent model malaria parasite and phenotypic analysis during life cycle progression revealed a non-vital role in vivo. Our findings suggest that plasmoredoxin fulfils a specialized and dispensable role for Plasmodium and highlights the need for target validation to inform drug development strategies.http://www.bibsonomy.org/bibtex/2b5fd6712f1a844b98b42a4084bc69b44/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Animals Antimalarials Biological_Transport Cell_Line Combination Drug_Resistance Drug_Therapy Glutathione_Reductase Humans IFZ Inbred_BALB_C Malaria Mice Naphthalenes Parasitic_Sensitivity_Tests Plasmodium_berghei Plasmodium_falciparum Structure-Activity_Relationship Tumor chloroquine <span class="authorEditorList"><a href="/author/Friebolin">Wolfgang Friebolin</a>, <a href="/author/Jannack">Beate Jannack</a>, <a href="/author/Wenzel">Nicole Wenzel</a>, <a href="/author/Furrer">Julien Furrer</a>, <a href="/author/Oeser">Thomas Oeser</a>, <a href="/author/Sanchez">P. Cecilia Sanchez</a>, <a href="/author/Lanzer">Michael Lanzer</a>, <a href="/author/Yardley">Vanessa Yardley</a>, <a href="/author/Becker">Katja Becker</a>, and <a href="/author/Davioud-Charvet">Elisabeth Davioud-Charvet</a> </span><em>J Med Chem</em> <em>51(5):1260-1277</em> (<em>2008/03/13/</em>)Tue Oct 14 16:07:18 CEST 2008J Med Chem51260-1277Antimalarial dual drugs based on potent inhibitors of glutathione reductase from Plasmodium falciparum512008/03/13/Animals Antimalarials Biological_Transport Cell_Line Combination Drug_Resistance Drug_Therapy Glutathione_Reductase Humans IFZ Inbred_BALB_C Malaria Mice Naphthalenes Parasitic_Sensitivity_Tests Plasmodium_berghei Plasmodium_falciparum Structure-Activity_Relationship Tumor chloroquine Plasmodium parasites are exposed to higher fluxes of reactive oxygen species and need high activities of intracellular antioxidant systems providing a steady glutathione flux. As a future generation of dual drugs, 18 naphthoquinones and phenols (or their reduced forms) containing three different linkers between the 4-aminoquinoline core and the redox active component were synthesized. Their antimalarial effects have been characterized in parasite assays using chloroquine-sensitive and -resistant strains of Plasmodium, alone or in drug combination, and in the Plasmodium berghei rodent model. In particular, two tertiary amides 34 and 36 showed potent antimalarial activity in the low nanomolar range against CQ-resistant parasites. The ability to compete both for (Fe (III))protoporphyrin and for chloroquine transporter was determined. The data are consistent with the presence of a carrier for uptake of the short chloroquine analogue 2 but not for the potent antimalarial amide 34, suggestinhttp://www.bibsonomy.org/bibtex/26df645811ef0bb6960d1c47ce69d8409/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Aerobiosis Animals Binding_Sites Disulfides Humans Hydrogen-Ion_Concentration IFZ Kinetics Methylene_Blue Oxidation-Reduction Oxidoreductases Plasmodium_falciparum Protozoan_Proteins Substrate_Specificity <span class="authorEditorList"><a href="/author/Buchholz">Kathrin Buchholz</a>, <a href="/author/Schirmer">Heiner R. Schirmer</a>, <a href="/author/Eubel">K. Jana Eubel</a>, <a href="/author/Akoachere">B. Monique Akoachere</a>, <a href="/author/Dandekar">Thomas Dandekar</a>, <a href="/author/Becker">Katja Becker</a>, and <a href="/author/Gromer">Stephan Gromer</a> </span><em>Antimicrob Agents Chemother</em> <em>52(1):183-191</em> (<em>2008/01//</em>)Tue Oct 14 16:07:18 CEST 2008Antimicrob Agents Chemother1183-191Interactions of methylene blue with human disulfide reductases and their orthologues from Plasmodium falciparum522008/01//Aerobiosis Animals Binding_Sites Disulfides Humans Hydrogen-Ion_Concentration IFZ Kinetics Methylene_Blue Oxidation-Reduction Oxidoreductases Plasmodium_falciparum Protozoan_Proteins Substrate_Specificity Methylene blue (MB) has experienced a renaissance mainly as a component of drug combinations against Plasmodium falciparum malaria. Here, we report biochemically relevant pharmacological data on MB such as rate constants for the uncatalyzed reaction of MB at pH 7.4 with cellular reductants like NAD(P)H (k = 4 M(-1) s(-1)), thioredoxins (k = 8.5 to 26 M(-1) s(-1)), dihydrolipoamide (k = 53 M(-1) s(-1)), and slowly reacting glutathione. As the disulfide reductases are prominent targets of MB, optical tests for enzymes reducing MB at the expense of NAD(P)H under aerobic conditions were developed. The product leucomethylene blue (leucoMB) is auto-oxidized back to MB at pH 7 but can be stabilized by enzymes at pH 5.0, which makes this colorless compound an interesting drug candidate. MB was found to be an inhibitor and/or a redox-cycling substrate of mammalian and P. falciparum disulfide reductases, with the kcat values ranging from 0.03 s(-1) to 10 s(-1) at 25 degrees C. Kinetic spectroscohttp://www.bibsonomy.org/bibtex/26bdd6d5206a79a250d7157bcfc34a724/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ Plasmodium_falciparum SELDI chloroquine mechanism_of_drug_action <span class="authorEditorList"><a href="/author/Koncarevic">Sasa Koncarevic</a>, <a href="/author/Bogumil">Ralf Bogumil</a>, and <a href="/author/Becker">Katja Becker</a> </span><em>PROTEOMICS</em> <em>7(5):711-721</em> (<em>2007</em>)Tue Oct 14 16:07:18 CEST 2008PROTEOMICS5711-721SELDI-TOF-MS analysis of chloroquine resistant and sensitive Plasmodium falciparum strains72007IFZ Plasmodium_falciparum SELDI chloroquine mechanism_of_drug_action The resistance of the malarial parasite Plasmodium falciparum to chloroquine represents an emerging problem since neither mode of drug action nor mechanisms of resistance are fully elucidated. We describe a protein expression profiling approach by SELDI-TOF-MS as a useful tool for studying the proteome of malarial parasites. Reproducible and complex protein profiles of the P. falciparum strains K1, Dd2, HB3 and 3D7 were measured on four array types. Hierarchical clustering led to a clear separation of the two major subgroups ��resistant" and ��sensitive" as well as of the four parasite strains. Our study delivers sets of regulated proteins derived from extensive comparative analyses of 64 P.falciparum protein profiles. A group of 12 peaks reflecting proteome changes under chloroquine treatment and a set of 10 potential chloroquine resistance markers were defined. Three of these regulated peaks were preparatively enriched, purified and identified. They were shown to represent the plasmohttp://www.bibsonomy.org/bibtex/26be732b9e6fd4a0342d646b1d4548c57/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span class="authorEditorList"><a href="/author/?"> ?</a> </span><em>e.velop&#034; 52 Internetmagazin der Bundesregierung zur Entwicklungspolitik</em> (<em>2007</em>)Tue Oct 14 16:07:18 CEST 2008e.velop" 52 (Internetmagazin der Bundesregierung zur Entwicklungspolitik)Warum haben Kinder in Afrika so oft Fieber?522007IFZ imported http://www.bibsonomy.org/bibtex/298fc799baaf6683cce2261568661c055/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ cancer chemotherapy inhibitor redox_sensitivity reductase thioredoxin <span class="authorEditorList"><a href="/author/Urig">Sabine Urig</a>, and <a href="/author/Becker">Katja Becker</a> </span><em>SEMINARS IN CANCER BIOLOGY</em> <em>16(6):452-465</em> (<em>2006</em>)Tue Oct 14 16:07:18 CEST 2008SEMINARS IN CANCER BIOLOGY6452-465On the potential of thioredoxin reductase inhibitors for cancer therapy162006IFZ cancer chemotherapy inhibitor redox_sensitivity reductase thioredoxin Thioredoxin reductase (TrxR)-as part of a major thiol regulating system-allows redox metabolism to adjust to cellular requirements. Therefore, changes at the redox level reflect as a pars pro toto changes concerning the entire cell. Three different TrxR isoenzymes, TrxR1 as cytosolic, TrxR2 as mitochondrial, and TrxR3 as testis-specific thiol regulator are known. All three enzymes contain a reactive and solvent accessible selenocysteine residue which is located on a flexible C-terminal arm of the protein. This selenocysteine is essentially involved in the catalytic cycle of TrxR and thus represents an attractive binding site for inhibitors. Many tumor cells have elevated TrxR levels and TrxR has been shown to play a major role in drug resistance. Inhibition of TrxR and its related redox reactions may thus contribute to a successful single, combinatory or adjuvant cancer therapy. A great number of effective natural and synthetic TrxR inhibitors are now available possessing antitumor pothttp://www.bibsonomy.org/bibtex/2950f50c2f369b21dbf7e9fcc5af989bd/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span class="authorEditorList"><a href="/author/Buchholz">Kathrin Buchholz</a>, <a href="/author/Matuschewski">Kai Matuschewski</a>, <a href="/author/Schirmer">Heiner R. Schirmer</a>, and <a href="/author/Becker">Katja Becker</a> </span><em>INTERNATIONAL JOURNAL FOR PARASITOLOGY</em> <em>38(Suppl. 1):S37</em> (<em>2008</em>)Tue Oct 14 16:07:18 CEST 2008INTERNATIONAL JOURNAL FOR PARASITOLOGYSuppl. 1S37Functional characterization of Plasmodium redoxrelated enzymes382008IFZ imported http://www.bibsonomy.org/bibtex/2c072e353590f0dd3fcaa54cff28c17a0/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span class="authorEditorList"><a href="/author/Buchholz">Kathrin Buchholz</a>, <a href="/author/Mailu">Boniface Mailu</a>, <a href="/author/Schirmer">Heiner R. Schirmer</a>, and <a href="/author/Becker">Katja Becker</a> </span><em>Frontiers in Drug Design and Discovery</em> (<em>2007</em>)Tue Oct 14 16:07:18 CEST 2008Frontiers in Drug Design and Discovery225-255Structure-based drug development against malaria32007IFZ imported http://www.bibsonomy.org/bibtex/215e69ea67a17d90be5bc2317eb09aff3/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span class="authorEditorList"><a href="/author/?"> ?</a> </span><em>INTERNATIONAL JOURNAL FOR PARASITOLOGY</em> <em>38(Suppl. 1):S28</em> (<em>2008</em>)Tue Oct 14 16:07:18 CEST 2008INTERNATIONAL JOURNAL FOR PARASITOLOGYSuppl. 1S28Quantitative proteomics of Plasmodium falciparum protein expression following drug exposure382008IFZ imported http://www.bibsonomy.org/bibtex/2779c9c2f3b4c8f40238339774a3d4832/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span class="authorEditorList"><a href="/author/Morin">Christophe Morin</a>, <a href="/author/Besset">Tatiana Besset</a>, <a href="/author/Moutet">Jean-Claude Moutet</a>, <a href="/author/Fayolle">Martine Fayolle</a>, <a href="/author/Br�ckner">Margit Br�ckner</a>, <a href="/author/Limosin">Dani?le Limosin</a>, <a href="/author/Becker">Katja Becker</a>, and <a href="/author/Davioud-Charvet">Elisabeth Davioud-Charvet</a> </span><em>Org Biomol Chem</em> <em>6(15):2731-2742</em> (<em>2008/08/07/</em>)Tue Oct 14 16:07:18 CEST 2008Org Biomol Chem152731-2742The aza-analogues of 1,4-naphthoquinones are potent substrates and inhibitors of plasmodial thioredoxin and glutathione reductases and of human erythrocyte glutathione reductase62008/08/07/IFZ imported Various aza-analogues of 1,4-naphthoquinone and menadione were prepared and tested as inhibitors and substrates of the plasmodial thioredoxin and glutathione reductases as well as the human glutathione reductase. The replacement of one to two carbons at the phenyl ring of the 1,4-naphthoquinone core by one to two nitrogen atoms led to an increased oxidant character of the molecules in accordance with both the redox potential values and the substrate efficiencies. Compared to the 1,4-naphthoquinone and menadione, the quinoline-5,8-dione 1 and both quinoxaline-5,8-diones 5 and 6 behaved as the most efficient subversive substrates of the three NADPH-dependent disulfide reductases tested. Modulation of these parameters was observed by alkylation of the aza-naphthoquinone core.http://www.bibsonomy.org/bibtex/208e03de016eac0326ebb47c3922bbc3d/nutribiochemnutribiochem2008-10-14T16:07:18+02:002&#039;-disulfonic_Acid 4-Acetamido-4&#039;-isothiocyanatostilbene-2 Allyl_Compounds Anticarcinogenic_Agents Cell_Cycle Cell_Line Cell_Proliferation Disulfides Dose-Response_Relationship Drug Glutathione Glutathione_Transferase Humans IFZ Oxidation-Reduction Sulfur_Compounds Thioredoxin-Disulfide_Reductase Thioredoxins Tumor Up-Regulation glutathione_peroxidase isothiocyanates <span class="authorEditorList"><a href="/author/Hu">Ying Hu</a>, <a href="/author/Urig">Sabine Urig</a>, <a href="/author/Koncarevic">Sasa Koncarevic</a>, <a href="/author/Wu">Xinjiang Wu</a>, <a href="/author/Fischer">Marina Fischer</a>, <a href="/author/Rahlfs">Stefan Rahlfs</a>, <a href="/author/Mersch-Sundermann">Volker Mersch-Sundermann</a>, and <a href="/author/Becker">Katja Becker</a> </span><em>Biol Chem</em> <em>388(10):1069-1081</em> (<em>2007/10//</em>)Tue Oct 14 16:07:18 CEST 2008Biol Chem101069-1081Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents3882007/10//2'-disulfonic_Acid 4-Acetamido-4'-isothiocyanatostilbene-2 Allyl_Compounds Anticarcinogenic_Agents Cell_Cycle Cell_Line Cell_Proliferation Disulfides Dose-Response_Relationship Drug Glutathione Glutathione_Transferase Humans IFZ Oxidation-Reduction Sulfur_Compounds Thioredoxin-Disulfide_Reductase Thioredoxins Tumor Up-Regulation glutathione_peroxidase isothiocyanates We studied the effects of sulfur-containing chemopreventive agents, including allyl sulfides and isothiocyanates, on human redox networks. Isothiocyanates inhibited isolated redox-active enzymes in a time- and dose-dependent manner. As shown for the most active compound, benzyl isothiocyanate (BITC), on thioredoxin reductase, the inhibition has an initial competitive part (Ki=6.1+/-1.0 microM) followed by a time-dependent irreversible inhibition (k2=72.8+/-25.5 M(-1) s(-1)). Also, glutathione reductase and glutathione S-transferase were irreversibly modified by BITC. Sulforaphane led to irreversible inhibition of the studied redox enzymes, but with 5-10 times lower k2 values. In contrast, allyl sulfides had only moderate effects on the tested enzymes. However, diallyl disulfide was found to react directly with reduced glutathione (k2=100 M(-2) s(-1)). This reaction might contribute to enhanced oxidative stress and the induction of the selenoprotein glutathione peroxidase as determined http://www.bibsonomy.org/bibtex/2678af63d13353f09e47f49eeee29f469/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Apoptosis Carcinoma Cell_Count Cell_Cycle Cell_Proliferation Cultured Dose-Response_Relationship Drug Genetic Glutathione Humans IFZ Lung_Neoplasms Messenger Non-Small-Cell_Lung Oxidation-Reduction Phosphotransferases RNA Reverse_Transcriptase_Polymerase_Chain_Reaction Sensitivity_and_Specificity Stilbenes Structure-Activity_Relationship Transcription Tumor_Cells glutathione_peroxidase <span class="authorEditorList"><a href="/author/Hu">Ying Hu</a>, <a href="/author/Rahlfs">Stefan Rahlfs</a>, <a href="/author/Mersch-Sundermann">Volker Mersch-Sundermann</a>, and <a href="/author/Becker">Katja Becker</a> </span><em>Biol Chem</em> <em>388(2):207-219</em> (<em>2007/02//</em>)Tue Oct 14 16:07:18 CEST 2008Biol Chem2207-219Resveratrol modulates mRNA transcripts of genes related to redox metabolism and cell proliferation in non-small-cell lung carcinoma cells3882007/02//Apoptosis Carcinoma Cell_Count Cell_Cycle Cell_Proliferation Cultured Dose-Response_Relationship Drug Genetic Glutathione Humans IFZ Lung_Neoplasms Messenger Non-Small-Cell_Lung Oxidation-Reduction Phosphotransferases RNA Reverse_Transcriptase_Polymerase_Chain_Reaction Sensitivity_and_Specificity Stilbenes Structure-Activity_Relationship Transcription Tumor_Cells glutathione_peroxidase Resveratrol is a polyphenolic chemopreventive agent that has been shown to influence cellular redox reactions. As a systematic approach to elucidating the complex effects of resveratrol on eukaryotic cells, we studied its dose-dependent effects on the transcript levels of genes and activities of enzymes related to redox metabolism, cell cycle regulation, and apoptotic cascades in the cancer cell line A549. Glutathione peroxidase (GPx)1 mRNA levels, as well as GPx and thioredoxin reductase (TrxR) activities, were significantly increased after resveratrol treatment, whereas total glutathione concentrations decreased. Increased transcript levels were also detected for selenophosphate synthetase 2 and superoxide dismutase 2. However, mRNA levels of thioredoxin, TrxR, glutathione reductase, glutathione S-transferase, superoxide dismutase 1, and catalase were not altered. Among the 12 genes studied that are related to the cell cycle, differentiation and apoptosis, mRNA levels of six genes, ihttp://www.bibsonomy.org/bibtex/24cd883fd4676fcbf70bc4e397511dbf0/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Alleles Amino_Acid_Substitution Cataract Child Codon Erythrocytes Favism Female Genetic_Diseases Glutathione_Reductase Heterozygote Humans IFZ Inborn Infant Jaundice Leukocytes Male Middle_Aged Neonatal Newborn Nonsense Preschool Protein_Structure Quaternary Sequence_Deletion Tertiary <span class="authorEditorList"><a href="/author/Kamerbeek">M. Nanne Kamerbeek</a>, <a href="/author/van Zwieten">Rob van Zwieten</a>, <a href="/author/Boer">Martin Boer</a>, <a href="/author/Morren">Gert Morren</a>, <a href="/author/Vuil">Herma Vuil</a>, <a href="/author/Bannink">Natalja Bannink</a>, <a href="/author/Lincke">Carsten Lincke</a>, <a href="/author/Dolman">M. Koert Dolman</a>, <a href="/author/Becker">Katja Becker</a>, <a href="/author/Schirmer">Heiner R. Schirmer</a>, <a href="/author/Gromer">Stephan Gromer</a>, and <a href="/author/Roos">Dirk Roos</a> </span><em>Blood</em> <em>109(8):3560-3566</em> (<em>2007/04/15/</em>)Tue Oct 14 16:07:18 CEST 2008Blood83560-3566Molecular basis of glutathione reductase deficiency in human blood cells1092007/04/15/Alleles Amino_Acid_Substitution Cataract Child Codon Erythrocytes Favism Female Genetic_Diseases Glutathione_Reductase Heterozygote Humans IFZ Inborn Infant Jaundice Leukocytes Male Middle_Aged Neonatal Newborn Nonsense Preschool Protein_Structure Quaternary Sequence_Deletion Tertiary Hereditary glutathione reductase (GR) deficiency was found in only 2 cases when testing more than 15 000 blood samples. We have investigated the blood cells of 2 patients (1a and 1b) in a previously described family suffering from favism and cataract and of a novel patient (2) presenting with severe neonatal jaundice. Red blood cells and leukocytes of the patients in family 1 did not contain any GR activity, and the GR protein was undetectable by Western blotting. Owing to a 2246-bp deletion in the patients' DNA, translated GR is expected to lack almost the complete dimerization domain, which results in unstable and inactive enzyme. The red blood cells from patient 2 did not exhibit GR activity either, but the patient's leukocytes contained some residual activity that correlated with a weak protein expression. Patient 2 was found to be a compound heterozygote, with a premature stop codon on one allele and a substitution of glycine 330, a highly conserved residue in the superfamily of Nhttp://www.bibsonomy.org/bibtex/2e50b48ede2d548f29c9be36590f6947a/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Animals Biopolymers Dimerization Electrophoresis Glutathione Glutathione_Transferase IFZ Plasmodium_falciparum Polyacrylamide_Gel Protein_Conformation Protein_Denaturation Recombinant_Proteins <span class="authorEditorList"><a href="/author/Tripathi">Timir Tripathi</a>, <a href="/author/Rahlfs">Stefan Rahlfs</a>, <a href="/author/Becker">Katja Becker</a>, and <a href="/author/Bhakuni">Vinod Bhakuni</a> </span><em>BMC Struct Biol</em> (<em>2007</em>)Tue Oct 14 16:07:18 CEST 2008BMC Struct Biol67-67Glutathione mediated regulation of oligomeric structure and functional activity of Plasmodium falciparum glutathione S-transferase72007Animals Biopolymers Dimerization Electrophoresis Glutathione Glutathione_Transferase IFZ Plasmodium_falciparum Polyacrylamide_Gel Protein_Conformation Protein_Denaturation Recombinant_Proteins BACKGROUND: In contrast to many other organisms, the malarial parasite Plasmodium falciparum possesses only one typical glutathione S-transferase. This enzyme, PfGST, cannot be assigned to any of the known GST classes and represents a most interesting target for antimalarial drug development. The PfGST under native conditions forms non-covalently linked higher aggregates with major population (approximately 98%) being tetramer. However, in the presence of 2 mM GSH, a dimer of PfGST is observed. Recently reported study on binding and catalytic properties of PfGST indicated a GSH dependent low-high affinity transition with simultaneous binding of two GSH molecules to PfGST dimer suggesting that GSH binds to low affinity inactive enzyme dimer converting it to high affinity functionally active dimer. In order to understand the role of GSH in tetramer-dimer transition of PfGST as well as in modulation of functional activity of the enzyme, detailed structural, functional and stability studiehttp://www.bibsonomy.org/bibtex/2482c03361f814d195909dd986d35fd68/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Amino_Acid Amino_Acid_Sequence Animals Chemical Dimerization Disulfides Drosophila_melanogaster IFZ Kinetics Models Molecular Molecular_Sequence_Data Mutagenesis Peroxidases Peroxiredoxins Sequence_Homology Site-Directed Substrate_Specificity Thioredoxins glutathione_peroxidase <span class="authorEditorList"><a href="/author/?"> ?</a> </span><em>J Mol Biol</em> <em>365(4):1033-1046</em> (<em>2007/01/26/</em>)Tue Oct 14 16:07:18 CEST 2008J Mol Biol41033-1046The thioredoxin specificity of Drosophila GPx: a paradigm for a peroxiredoxin-like mechanism of many glutathione peroxidases3652007/01/26/Amino_Acid Amino_Acid_Sequence Animals Chemical Dimerization Disulfides Drosophila_melanogaster IFZ Kinetics Models Molecular Molecular_Sequence_Data Mutagenesis Peroxidases Peroxiredoxins Sequence_Homology Site-Directed Substrate_Specificity Thioredoxins glutathione_peroxidase Some members of the glutathione peroxidase (GPx) family have been reported to accept thioredoxin as reducing substrate. However, the selenocysteine-containing ones oxidise thioredoxin (Trx), if at all, at extremely slow rates. In contrast, the Cys homolog of Drosophila melanogaster exhibits a clear preference for Trx, the net forward rate constant, k'(+2), for reduction by Trx being 1.5x10(6) M(-1) s(-1), but only 5.4 M(-1) s(-1) for glutathione. Like other CysGPxs with thioredoxin peroxidase activity, Drosophila melanogaster (Dm)GPx oxidized by H(2)O(2) contained an intra-molecular disulfide bridge between the active-site cysteine (C45; C(P)) and C91. Site-directed mutagenesis of C91 in DmGPx abrogated Trx peroxidase activity, but increased the rate constant for glutathione by two orders of magnitude. In contrast, a replacement of C74 by Ser or Ala only marginally affected activity and specificity of DmGPx. Furthermore, LC-MS/MS analysis of oxidized DmGPx exposed to a reduced Trx C35Shttp://www.bibsonomy.org/bibtex/2ca1c6a601bdcd01ec74326eee3a78393/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Animals Erythrocytes Hemeproteins Humans IFZ Malaria Molecular_Structure Plasmodium_falciparum Raman Spectrum_Analysis Trophozoites <span class="authorEditorList"><a href="/author/Frosch">Torsten Frosch</a>, <a href="/author/Koncarevic">Sasa Koncarevic</a>, <a href="/author/Zedler">Linda Zedler</a>, <a href="/author/Schmitt">Michael Schmitt</a>, <a href="/author/Schenzel">Karla Schenzel</a>, <a href="/author/Becker">Katja Becker</a>, and <a href="/author/Popp">J�rgen Popp</a> </span><em>J Phys Chem B</em> <em>111(37):11047-11056</em> (<em>2007/09/20/</em>)Tue Oct 14 16:07:18 CEST 2008J Phys Chem B3711047-11056In situ localization and structural analysis of the malaria pigment hemozoin1112007/09/20/Animals Erythrocytes Hemeproteins Humans IFZ Malaria Molecular_Structure Plasmodium_falciparum Raman Spectrum_Analysis Trophozoites Raman microspectroscopy was applied for an in situ localization of the malaria pigment hemozoin in Plasmodium falciparum-infected erythrocytes. The Raman spectra (lambdaexc=633 nm) of hemozoin show very intense signals with a very good signal-to-noise ratio. These in situ Raman signals of hemozoin were compared to Raman spectra of extracted hemozoin, of the synthetic analogue beta-hematin, and of hematin and hemin. beta-Hematin was synthesized according to the acid-catalyzed dehydration of hematin and the anhydrous dehydrohalogenation of hemin which lead to good crystals with lengths of about 5-30 microm. The Raman spectra (lambdaexc=1064 nm) of hemozoin and beta-hematin show almost identical behaviors, while some low wavenumber modes might be used to distinguish between the morphology of differently synthesized beta-hematin samples. The intensity pattern of the resonance Raman spectra (lambdaexc=568 nm) of hemozoin and beta-hematin differ significantly from those of hematin and hemin.http://www.bibsonomy.org/bibtex/2b1ec0fa05f47269651b25ab8ed7eaad5/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Animal Animals Brain_Neoplasms Breast_Neoplasms Cell_Growth_Processes Citric_Acid_Cycle Disease_Models Energy_Metabolism Female Glutathione Glycolysis Humans IFZ Mice Mitochondria Oxidation-Reduction Oxygen_Consumption Pentose_Phosphate_Pathway Proteomics SCID <span class="authorEditorList"><a href="/author/Chen">I. Emily Chen</a>, <a href="/author/Hewel">Johannes Hewel</a>, <a href="/author/Krueger">S. Joseph Krueger</a>, <a href="/author/Tiraby">Claire Tiraby</a>, <a href="/author/Weber">R. Martin Weber</a>, <a href="/author/Kralli">Anastasia Kralli</a>, <a href="/author/Becker">Katja Becker</a>, <a href="/author/Yates">R. John Yates</a>, and <a href="/author/Felding-Habermann">Brunhilde Felding-Habermann</a> </span><em>Cancer Res</em> <em>67(4):1472-1486</em> (<em>2007/02/15/</em>)Tue Oct 14 16:07:18 CEST 2008Cancer Res41472-1486Adaptation of energy metabolism in breast cancer brain metastases672007/02/15/Animal Animals Brain_Neoplasms Breast_Neoplasms Cell_Growth_Processes Citric_Acid_Cycle Disease_Models Energy_Metabolism Female Glutathione Glycolysis Humans IFZ Mice Mitochondria Oxidation-Reduction Oxygen_Consumption Pentose_Phosphate_Pathway Proteomics SCID Brain metastases are among the most feared complications in breast cancer, as no therapy exists that prevents or eliminates breast cancer spreading to the brain. New therapeutic strategies depend on specific knowledge of tumor cell properties that allow breast cancer cell growth within the brain tissue. To provide information in this direction, we established a human breast cancer cell model for brain metastasis based on circulating tumor cells from a breast cancer patient and variants of these cells derived from bone or brain lesions in immunodeficient mice. The brain-derived cells showed an increased potential for brain metastasis in vivo and exhibited a unique protein expression profile identified by large-scale proteomic analysis. This protein profile is consistent with either a selection of predisposed cells or bioenergetic adaptation of the tumor cells to the unique energy metabolism of the brain. Increased expression of enzymes involved in glycolysis, tricarboxylic acid cycle, ahttp://www.bibsonomy.org/bibtex/2f7da19c92c1723c8c603d5019cf616ec/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Amino_Acid Amino_Acid_Sequence Animals Circular_Dichroism Glutaredoxins IFZ Molecular_Sequence_Data Molecular_Weight Plasmodium_falciparum Protein_Binding Protein_Denaturation Protons Protozoan_Proteins Sequence_Homology Temperature <span class="authorEditorList"><a href="/author/Tripathi">Timir Tripathi</a>, <a href="/author/Rahlfs">Stefan Rahlfs</a>, <a href="/author/Becker">Katja Becker</a>, and <a href="/author/Bhakuni">Vinod Bhakuni</a> </span><em>Biochim Biophys Acta</em> <em>1784(6):946-952</em> (<em>2008/06//</em>)Tue Oct 14 16:07:18 CEST 2008Biochim Biophys Acta6946-952Structural and stability characteristics of a monothiol glutaredoxin: glutaredoxin-like protein 1 from Plasmodium falciparum17842008/06//Amino_Acid Amino_Acid_Sequence Animals Circular_Dichroism Glutaredoxins IFZ Molecular_Sequence_Data Molecular_Weight Plasmodium_falciparum Protein_Binding Protein_Denaturation Protons Protozoan_Proteins Sequence_Homology Temperature Recently discovered monothiol glutaredoxins with CXXS-active site sequence share a common structural motif and biochemical mechanism of action and are involved in multiple cellular functions. Here we report first studies on the structural and stability characterization of a monothiol glutaredoxin, in particular--PfGLP1. Our results demonstrate that in the native conformation, the enzyme has a compact core structure with a relatively flexible N-terminal portion having an open configuration. Comparative functional studies with the full-length and N-terminal truncated protein demonstrate that the flexible N-terminal portion does not play any significant role in functional activity of the protein. In contrast to other Grxs, PfGLP1 does not contain a Fe-S cluster. The pH dependent studies demonstrate that the protein is resistant to alkaline pH but highly sensitive to acidic pH and undergoes significant unfolding between pH 4 and 5. However, acidic conditions also do not induce complete unf