http://www.bibsonomy.org/burst/group/bibliothek2.0BibSonomy BuRST Feed for /group/bibliothek2.02008-10-16T09:11:56+02:00Cinearchivhttp://www.bibsonomy.org/bibtex/245ae9616f7c7e480384d43cb2f6aec4d/pertinaxpertinax2008-10-15T16:16:13+02:00collaborative tagging <span style="color:#555555;">Adam <a href="http://www.bibsonomy.org/author/Mathes">Mathes</a> </span>(<em>2004</em>)Wed Oct 15 16:16:13 CEST 2008Folksonomies - Cooperative Classification and Communication Through Shared Metadata2004collaborative tagging http://www.bibsonomy.org/bibtex/2b54f6557893e3ab9d1eb83b0baeb136e/pertinaxpertinax2008-10-15T16:14:52+02:00social bokkmarking <span style="color:#555555;">Andreas <a href="http://www.bibsonomy.org/author/Hotho">Hotho</a> </span><em>Seite26-38. </em><em>Oldenbourg Verlag, </em><em>M&#252;nchen, </em>(<em>2008</em>)Wed Oct 15 16:14:52 CEST 2008MünchenWeb 2.0 in der Unternehmenspraxis: Grundlagen, Fallstudien und Trends zum Einsatz von Social Software26-38Social Bookmarking2008social bokkmarking Tagging Bibliothekhttp://www.bibsonomy.org/bibtex/23d6e0e00b9c15cff86def6fcdf27ebc9/pertinaxpertinax2008-10-14T17:07:06+02:00imported <span style="color:#555555;"> </span>(<em>2008</em>)Tue Oct 14 17:07:06 CEST 2008Der Autor diskutiert die Vor-und Nachteile von Collaborative tagging im Kontext der bibliothekarischen Sacherschlie ung. Ein zweiter Schwerpunkt liegt in der Auswertung des sozialen Verhaltens der Nutzer des rezensionstools der Universit tsbibliothek Mannheim2008imported http://www.bibsonomy.org/bibtex/2b5fd6712f1a844b98b42a4084bc69b44/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Combination Animals Humans Structure-Activity_Relationship Glutathione_Reductase Plasmodium_falciparum Malaria Mice Inbred_BALB_C Antimalarials Naphthalenes IFZ Tumor Parasitic_Sensitivity_Tests Cell_Line Plasmodium_berghei chloroquine Drug_Resistance Drug_Therapy Biological_Transport <span style="color:#555555;">Wolfgang <a href="http://www.bibsonomy.org/author/Friebolin">Friebolin</a> und Beate <a href="http://www.bibsonomy.org/author/Jannack">Jannack</a> und Nicole <a href="http://www.bibsonomy.org/author/Wenzel">Wenzel</a> und Julien <a href="http://www.bibsonomy.org/author/Furrer">Furrer</a> und Thomas <a href="http://www.bibsonomy.org/author/Oeser">Oeser</a> und P. <a href="http://www.bibsonomy.org/author/Cecilia Sanchez">Cecilia Sanchez</a> und Michael <a href="http://www.bibsonomy.org/author/Lanzer">Lanzer</a> und Vanessa <a href="http://www.bibsonomy.org/author/Yardley">Yardley</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> und Elisabeth <a href="http://www.bibsonomy.org/author/Davioud-Charvet">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/Combination Animals Humans Structure-Activity_Relationship Glutathione_Reductase Plasmodium_falciparum Malaria Mice Inbred_BALB_C Antimalarials Naphthalenes IFZ Tumor Parasitic_Sensitivity_Tests Cell_Line Plasmodium_berghei chloroquine Drug_Resistance Drug_Therapy Biological_Transport 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+02:00Animals Humans Plasmodium_falciparum Binding_Sites Disulfides Oxidation-Reduction IFZ Kinetics Substrate_Specificity Aerobiosis Hydrogen-Ion_Concentration Methylene_Blue Oxidoreductases Protozoan_Proteins <span style="color:#555555;">Kathrin <a href="http://www.bibsonomy.org/author/Buchholz">Buchholz</a> und Heiner R. <a href="http://www.bibsonomy.org/author/Schirmer">Schirmer</a> und K. <a href="http://www.bibsonomy.org/author/Jana Eubel">Jana Eubel</a> und B. <a href="http://www.bibsonomy.org/author/Monique Akoachere">Monique Akoachere</a> und Thomas <a href="http://www.bibsonomy.org/author/Dandekar">Dandekar</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> und Stephan <a href="http://www.bibsonomy.org/author/Gromer">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//Animals Humans Plasmodium_falciparum Binding_Sites Disulfides Oxidation-Reduction IFZ Kinetics Substrate_Specificity Aerobiosis Hydrogen-Ion_Concentration Methylene_Blue Oxidoreductases Protozoan_Proteins 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+02:00SELDI IFZ mechanism_of_drug_action Plasmodium_falciparum chloroquine <span style="color:#555555;">Sasa <a href="http://www.bibsonomy.org/author/Koncarevic">Koncarevic</a> und Ralf <a href="http://www.bibsonomy.org/author/Bogumil">Bogumil</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">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 strains72007SELDI IFZ mechanism_of_drug_action Plasmodium_falciparum chloroquine 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/298fc799baaf6683cce2261568661c055/nutribiochemnutribiochem2008-10-14T16:07:18+02:00thioredoxin reductase IFZ redox_sensitivity inhibitor chemotherapy cancer <span style="color:#555555;">Sabine <a href="http://www.bibsonomy.org/author/Urig">Urig</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">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 therapy162006thioredoxin reductase IFZ redox_sensitivity inhibitor chemotherapy cancer 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/2c072e353590f0dd3fcaa54cff28c17a0/nutribiochemnutribiochem2008-10-14T16:07:18+02:00IFZ imported <span style="color:#555555;">Kathrin <a href="http://www.bibsonomy.org/author/Buchholz">Buchholz</a> und Boniface <a href="http://www.bibsonomy.org/author/Mailu">Mailu</a> und Heiner R. <a href="http://www.bibsonomy.org/author/Schirmer">Schirmer</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">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 style="color:#555555;"> </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 style="color:#555555;">Christophe <a href="http://www.bibsonomy.org/author/Morin">Morin</a> und Tatiana <a href="http://www.bibsonomy.org/author/Besset">Besset</a> und Jean-Claude <a href="http://www.bibsonomy.org/author/Moutet">Moutet</a> und Martine <a href="http://www.bibsonomy.org/author/Fayolle">Fayolle</a> und Margit <a href="http://www.bibsonomy.org/author/Br�ckner">Br&#65533;ckner</a> und Dani?le <a href="http://www.bibsonomy.org/author/Limosin">Limosin</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> und Elisabeth <a href="http://www.bibsonomy.org/author/Davioud-Charvet">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'-disulfonic_Acid glutathione_peroxidase Glutathione Humans Cell_Proliferation Disulfides Dose-Response_Relationship Thioredoxins Anticarcinogenic_Agents isothiocyanates Sulfur_Compounds Oxidation-Reduction Allyl_Compounds Cell_Cycle IFZ Tumor Drug Glutathione_Transferase Thioredoxin-Disulfide_Reductase Cell_Line Up-Regulation 4-Acetamido-4'-isothiocyanatostilbene-2 <span style="color:#555555;">Ying <a href="http://www.bibsonomy.org/author/Hu">Hu</a> und Sabine <a href="http://www.bibsonomy.org/author/Urig">Urig</a> und Sasa <a href="http://www.bibsonomy.org/author/Koncarevic">Koncarevic</a> und Xinjiang <a href="http://www.bibsonomy.org/author/Wu">Wu</a> und Marina <a href="http://www.bibsonomy.org/author/Fischer">Fischer</a> und Stefan <a href="http://www.bibsonomy.org/author/Rahlfs">Rahlfs</a> und Volker <a href="http://www.bibsonomy.org/author/Mersch-Sundermann">Mersch-Sundermann</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">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 glutathione_peroxidase Glutathione Humans Cell_Proliferation Disulfides Dose-Response_Relationship Thioredoxins Anticarcinogenic_Agents isothiocyanates Sulfur_Compounds Oxidation-Reduction Allyl_Compounds Cell_Cycle IFZ Tumor Drug Glutathione_Transferase Thioredoxin-Disulfide_Reductase Cell_Line Up-Regulation 4-Acetamido-4'-isothiocyanatostilbene-2 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+02:00glutathione_peroxidase Apoptosis Reverse_Transcriptase_Polymerase_Chain_Reaction Lung_Neoplasms Glutathione Humans Cultured Cell_Proliferation Oxidation-Reduction Phosphotransferases Sensitivity_and_Specificity IFZ Stilbenes Drug Cell_Count Tumor_Cells Structure-Activity_Relationship Transcription Dose-Response_Relationship Genetic Carcinoma Non-Small-Cell_Lung Cell_Cycle RNA Messenger <span style="color:#555555;">Ying <a href="http://www.bibsonomy.org/author/Hu">Hu</a> und Stefan <a href="http://www.bibsonomy.org/author/Rahlfs">Rahlfs</a> und Volker <a href="http://www.bibsonomy.org/author/Mersch-Sundermann">Mersch-Sundermann</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">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//glutathione_peroxidase Apoptosis Reverse_Transcriptase_Polymerase_Chain_Reaction Lung_Neoplasms Glutathione Humans Cultured Cell_Proliferation Oxidation-Reduction Phosphotransferases Sensitivity_and_Specificity IFZ Stilbenes Drug Cell_Count Tumor_Cells Structure-Activity_Relationship Transcription Dose-Response_Relationship Genetic Carcinoma Non-Small-Cell_Lung Cell_Cycle RNA Messenger 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/2e50b48ede2d548f29c9be36590f6947a/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Animals Recombinant_Proteins Polyacrylamide_Gel Electrophoresis Protein_Denaturation IFZ Glutathione Dimerization Glutathione_Transferase Biopolymers Plasmodium_falciparum Protein_Conformation <span style="color:#555555;">Timir <a href="http://www.bibsonomy.org/author/Tripathi">Tripathi</a> und Stefan <a href="http://www.bibsonomy.org/author/Rahlfs">Rahlfs</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> und Vinod <a href="http://www.bibsonomy.org/author/Bhakuni">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 Recombinant_Proteins Polyacrylamide_Gel Electrophoresis Protein_Denaturation IFZ Glutathione Dimerization Glutathione_Transferase Biopolymers Plasmodium_falciparum Protein_Conformation 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_Sequence Drosophila_melanogaster Animals glutathione_peroxidase Peroxiredoxins Dimerization Molecular_Sequence_Data Site-Directed Disulfides Chemical Thioredoxins Sequence_Homology Peroxidases Models Mutagenesis Amino_Acid IFZ Kinetics Substrate_Specificity Molecular <span style="color:#555555;"> </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_Sequence Drosophila_melanogaster Animals glutathione_peroxidase Peroxiredoxins Dimerization Molecular_Sequence_Data Site-Directed Disulfides Chemical Thioredoxins Sequence_Homology Peroxidases Models Mutagenesis Amino_Acid IFZ Kinetics Substrate_Specificity Molecular 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 Raman IFZ Humans Spectrum_Analysis Erythrocytes Hemeproteins Plasmodium_falciparum Malaria Molecular_Structure Trophozoites <span style="color:#555555;">Torsten <a href="http://www.bibsonomy.org/author/Frosch">Frosch</a> und Sasa <a href="http://www.bibsonomy.org/author/Koncarevic">Koncarevic</a> und Linda <a href="http://www.bibsonomy.org/author/Zedler">Zedler</a> und Michael <a href="http://www.bibsonomy.org/author/Schmitt">Schmitt</a> und Karla <a href="http://www.bibsonomy.org/author/Schenzel">Schenzel</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> und J&#65533;rgen <a href="http://www.bibsonomy.org/author/Popp">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 Raman IFZ Humans Spectrum_Analysis Erythrocytes Hemeproteins Plasmodium_falciparum Malaria Molecular_Structure 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+02:00Animals Citric_Acid_Cycle Energy_Metabolism Glutathione Humans SCID Animal Brain_Neoplasms Mitochondria Mice Breast_Neoplasms Oxidation-Reduction Cell_Growth_Processes Pentose_Phosphate_Pathway IFZ Proteomics Disease_Models Oxygen_Consumption Glycolysis Female <span style="color:#555555;">I. <a href="http://www.bibsonomy.org/author/Emily Chen">Emily Chen</a> und Johannes <a href="http://www.bibsonomy.org/author/Hewel">Hewel</a> und S. <a href="http://www.bibsonomy.org/author/Joseph Krueger">Joseph Krueger</a> und Claire <a href="http://www.bibsonomy.org/author/Tiraby">Tiraby</a> und R. <a href="http://www.bibsonomy.org/author/Martin Weber">Martin Weber</a> und Anastasia <a href="http://www.bibsonomy.org/author/Kralli">Kralli</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> und R. <a href="http://www.bibsonomy.org/author/John Yates">John Yates</a> und Brunhilde <a href="http://www.bibsonomy.org/author/Felding-Habermann">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/Animals Citric_Acid_Cycle Energy_Metabolism Glutathione Humans SCID Animal Brain_Neoplasms Mitochondria Mice Breast_Neoplasms Oxidation-Reduction Cell_Growth_Processes Pentose_Phosphate_Pathway IFZ Proteomics Disease_Models Oxygen_Consumption Glycolysis Female 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_Sequence Animals Protons Molecular_Sequence_Data Temperature Glutaredoxins Plasmodium_falciparum Protein_Binding Sequence_Homology Amino_Acid IFZ Protein_Denaturation Circular_Dichroism Molecular_Weight Protozoan_Proteins <span style="color:#555555;">Timir <a href="http://www.bibsonomy.org/author/Tripathi">Tripathi</a> und Stefan <a href="http://www.bibsonomy.org/author/Rahlfs">Rahlfs</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> und Vinod <a href="http://www.bibsonomy.org/author/Bhakuni">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_Sequence Animals Protons Molecular_Sequence_Data Temperature Glutaredoxins Plasmodium_falciparum Protein_Binding Sequence_Homology Amino_Acid IFZ Protein_Denaturation Circular_Dichroism Molecular_Weight Protozoan_Proteins 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 unfhttp://www.bibsonomy.org/bibtex/2d7f6838237ede031ae7ed91b15cf2178/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Animals glutathione_peroxidase Peroxiredoxins Humans Drug_Design Thioredoxins Catalase Sequence_Homology Amino_Acid Protozoa IFZ Glutathione_Transferase Protozoan_Infections Protozoan_Proteins <span style="color:#555555;">Marcel <a href="http://www.bibsonomy.org/author/Deponte">Deponte</a> und Stefan <a href="http://www.bibsonomy.org/author/Rahlfs">Rahlfs</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> </span><em>Subcell Biochem</em>(<em>2007</em>)Tue Oct 14 16:07:18 CEST 2008Subcell Biochem219-229Peroxiredoxin systems of protozoal parasites442007Animals glutathione_peroxidase Peroxiredoxins Humans Drug_Design Thioredoxins Catalase Sequence_Homology Amino_Acid Protozoa IFZ Glutathione_Transferase Protozoan_Infections Protozoan_Proteins Cellular redox metabolism is considered to be involved in the pathophysiology of diseases caused by protozoal parasites such as Toxoplasma, Trypanosoma, Leishmania, and Plasmodia. Redox reactions furthermore are thought to play a major role in the action of and the resistance to some clinically used antiparasitic drugs. Interestingly, in malarial parasites, the antioxidant enzymes catalase and glutathione peroxidase are absent which indicates a crucial role of the thioredoxin system in redox control. Besides a glutathione peroxidase-like thioredoxin peroxidase and a glutathione S-transferase with slight peroxidase activity, Plasmodium falciparum (the causative agent of tropical malaria) possesses four classical peroxiredoxins: Two peroxiredoxins of the typical 2-Cys Prx class, one 1-Cys peroxiredoxin with homology to the atypical 2-Cys Prx class, and a peroxiredoxin of the 1-Cys Prx class have been identified and partially characterized In our article we give an introduction to redox-bhttp://www.bibsonomy.org/bibtex/26093486f32244a6d56e220871c8e0959/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Enzyme_Inhibitors Animals Quaternary Humans Molecular_Sequence_Data thioredoxin_reductase_1 Protein_Structure Binding_Sites Models NADP X-Ray Oxidation-Reduction catalysis Cysteine IFZ Thioredoxin-Disulfide_Reductase Crystallography Molecular <span style="color:#555555;">Karin <a href="http://www.bibsonomy.org/author/Fritz-Wolf">Fritz-Wolf</a> und Sabine <a href="http://www.bibsonomy.org/author/Urig">Urig</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> </span><em>J Mol Biol</em><em>370(1):116-127</em>(<em>2007/06/29/</em>)Tue Oct 14 16:07:18 CEST 2008J Mol Biol1116-127The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis3702007/06/29/Enzyme_Inhibitors Animals Quaternary Humans Molecular_Sequence_Data thioredoxin_reductase_1 Protein_Structure Binding_Sites Models NADP X-Ray Oxidation-Reduction catalysis Cysteine IFZ Thioredoxin-Disulfide_Reductase Crystallography Molecular Human thioredoxin reductase (hTrxR) is a homodimeric flavoprotein crucially involved in the regulation of cellular redox reactions, growth and differentiation. The enzyme contains a selenocysteine residue at its C-terminal active site that is essential for catalysis. This redox center is located on a flexible arm, solvent-exposed and reactive towards electrophilic inhibitors, thus representing a target for antitumor drug development. During catalysis reducing equivalents are transferred from the cofactor NADPH to FAD, then to the N-terminal active site cysteine residues and from there to the flexible C-terminal part of the other subunit to be finally delivered to a variety of second substrates at the molecule's surface. Here we report the first crystal structure of hTrxR1 (Sec-->Cys) in complex with FAD and NADP(+) at a resolution of 2.8 A. From the crystals three different conformations of the carboxy-terminal arm could be deduced. The predicted movement of the arm is facilitated by thttp://www.bibsonomy.org/bibtex/2bc09854c1f58828be833d172d10fe684/nutribiochemnutribiochem2008-10-14T16:07:18+02:00Yeasts Enzyme_Inhibitors Animals Bacteria Recombinant_Proteins Species_Specificity Glutathione Humans Structure-Activity_Relationship Plasmodium_falciparum Malaria Binding_Sites Falciparum Drug_Design IFZ Allosteric_Regulation Kinetics Pyruvaldehyde Lactoylglutathione_Lyase Protozoan_Proteins <span style="color:#555555;">Marcel <a href="http://www.bibsonomy.org/author/Deponte">Deponte</a> und Nicole <a href="http://www.bibsonomy.org/author/Sturm">Sturm</a> und Sarah <a href="http://www.bibsonomy.org/author/Mittler">Mittler</a> und Max <a href="http://www.bibsonomy.org/author/Harner">Harner</a> und Hildegard <a href="http://www.bibsonomy.org/author/Mack">Mack</a> und Katja <a href="http://www.bibsonomy.org/author/Becker">Becker</a> </span><em>J Biol Chem</em><em>282(39):28419-28430</em>(<em>2007/09/28/</em>)Tue Oct 14 16:07:18 CEST 2008J Biol Chem3928419-28430Allosteric coupling of two different functional active sites in monomeric Plasmodium falciparum glyoxalase I2822007/09/28/Yeasts Enzyme_Inhibitors Animals Bacteria Recombinant_Proteins Species_Specificity Glutathione Humans Structure-Activity_Relationship Plasmodium_falciparum Malaria Binding_Sites Falciparum Drug_Design IFZ Allosteric_Regulation Kinetics Pyruvaldehyde Lactoylglutathione_Lyase Protozoan_Proteins Glyoxalase I (GloI) catalyzes the glutathione-dependent conversion of 2-oxoaldehydes to S-2-hydroxyacylglutathione derivatives. Studies on GloI from diverse organisms such as man, bacteria, yeast, and different parasites show striking differences among these potentially isofunctional enzymes as far as metal content and the number of active sites per subunit are concerned. So far, it is not known whether this structural variability is linked to catalytic or regulatory features in vivo. Here we show that recombinant GloI from the malaria parasite Plasmodium falciparum has a high- and a low-affinity binding site for the diastereomeric hemithioacetals formed by addition of glutathione to methylglyoxal. Both active sites of the monomeric enzyme are functional and have similar k(cat)(app) values. Proteolytic susceptibility studies and detailed analyses of the steady-state kinetics of active-site mutants suggest that both reaction centers can adopt two discrete conformations and are allosteri