The Experts below are selected from a list of 5928 Experts worldwide ranked by ideXlab platform
William N Hunter - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:Abstract Background: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine–glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. Results: The TR–trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH•••O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. Conclusions: The structure of the TR–trypanothione enzyme–substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:BACKGROUND: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine-glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. RESULTS: The TR-trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH***O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. CONCLUSIONS: The structure of the TR-trypanothione enzyme-substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
Charles S Bond - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:Abstract Background: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine–glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. Results: The TR–trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH•••O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. Conclusions: The structure of the TR–trypanothione enzyme–substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:BACKGROUND: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine-glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. RESULTS: The TR-trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH***O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. CONCLUSIONS: The structure of the TR-trypanothione enzyme-substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
B. Hentati - One of the best experts on this subject based on the ideXlab platform.
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Effects of date seed oil on normal human skin in vitro
European Journal of Dermatology, 2007Co-Authors: Ines Dammak, Sonia Boudaya, Fatma Ben Abdallah, A El Gaied, Hosam Attia, Leila Keskes, Souhail Besbes, Hamida Turki, B. HentatiAbstract:Oxidative stress has been implicated in various skin diseases through the generation of reactive oxygen species and the depletion of endogenous antioxidant systems. The administration of antioxidants or free radical scavengers is reportedly helpful, notably in order to enhance the healing process. We investigated the protective effect of a New Natural Product: date seed oil: (DSO) against hydrogen peroxide (H2O2)-induced oxidative stress, in terms of lipid peroxidation, depletion of endogenous antioxidant defense enzymes such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), one day after a 2 h exposure to H2O2, using human skin organ culture as an in vitro model. In the investigated model system, DSO has significant protective effect, by inhibition of damage caused by H2O2, endowing a radical scavenging ability. Treatment of skin with DSO inhibited H2O2-induced lipid peroxidation. In addition, this oil inhibited H2O2-induced depletion of antioxidant defense components, such as superoxide dismutase and catalase. We conclude that DSO could be useful in the attenuation of H2O2-induced oxidative stress-mediated skin diseases in human skin, possibly due to antioxidant properties.
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Date seed oil limit oxidative injuries induced by hydrogen peroxide in human skin organ culture
Biofactors, 2007Co-Authors: Ines Dammak, Sonia Boudaya, F B Abdallah, A El Gaied, Hosam Attia, Leila Keskes, Souhail Besbes, Hamida Turki, B. HentatiAbstract:The skin is chronically exposed to pro-oxidant agents, leading to the generation of reactive oxygen species (ROS). To protect the skin against an over-load of oxidant species, we studied the chemoprotective effect of one New Natural Product: "date seed oil: DSO". This oil may serve as a potential source of Natural antioxidants such as phenols and tocopherols. Here, the antioxidative potential of DSO was compared that of to extra virgin olive oil. Adult human skin was maintained in organ culture in the presence of the DSO and extra virgin olive oil before the addition of hydrogen peroxide (H2O2), in order to prevent the tissue from its oxidizing effects. Skin specimens were collected for histology and for melanin studies. In the investigated model system, DSO protects skin against oxidative injuries. It has a significant chemoprotective effect, by inhibition of damage caused by H_{2}O_{2} compared with specimens without such addition endowing with a radical scavenging ability. The various components from DSO were much more potent antioxidant and more free radical scavengers of the H2O2 than those of olive oil. Our study shows that topical DSO treatment of the skin stimulates events in the epidermis leading to repair skin damage possibly due to antioxidant synergisms.
Alan H Fairlamb - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:Abstract Background: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine–glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. Results: The TR–trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH•••O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. Conclusions: The structure of the TR–trypanothione enzyme–substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:BACKGROUND: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine-glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. RESULTS: The TR-trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH***O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. CONCLUSIONS: The structure of the TR-trypanothione enzyme-substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
Mark Cunningham - One of the best experts on this subject based on the ideXlab platform.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:Abstract Background: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine–glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. Results: The TR–trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH•••O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. Conclusions: The structure of the TR–trypanothione enzyme–substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
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crystal structure of trypanosoma cruzi trypanothione reductase in complex with trypanothione and the structure based discovery of New Natural Product inhibitors
Structure, 1999Co-Authors: Charles S Bond, Yihong Zhang, Matthew Berriman, Mark Cunningham, Alan H Fairlamb, William N HunterAbstract:BACKGROUND: Trypanothione reductase (TR) helps to maintain an intracellular reducing environment in trypanosomatids, a group of protozoan parasites that afflict humans and livestock in tropical areas. This protective function is achieved via reduction of polyamine-glutathione conjugates, in particular trypanothione. TR has been validated as a chemotherapeutic target by molecular genetics methods. To assist the development of New therapeutics, we have characterised the structure of TR from the pathogen Trypanosoma cruzi complexed with the substrate trypanothione and have used the structure to guide database searches and molecular modelling studies. RESULTS: The TR-trypanothione-disulfide structure has been determined to 2.4 A resolution. The chemical interactions involved in enzyme recognition and binding of substrate can be inferred from this structure. Comparisons with the related mammalian enzyme, glutathione reductase, explain why each enzyme is so specific for its own substrate. A CH***O hydrogen bond can occur between the active-site histidine and a carbonyl of the substrate. This interaction contributes to enzyme specificity and mechanism by producing an electronic induced fit when substrate binds. Database searches and molecular modelling using the substrate as a template and the active site as receptor have identified a class of cyclic-polyamine Natural Products that are novel TR inhibitors. CONCLUSIONS: The structure of the TR-trypanothione enzyme-substrate complex provides details of a potentially valuable drug target. This information has helped to identify a New class of enzyme inhibitors as novel lead compounds worthy of further development in the search for improved medicines to treat a range of parasitic infections.
