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B.k. Gudmundsdottir - One of the best experts on this subject based on the ideXlab platform.
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Structural evidence of intramolecular propeptide inhibition of the aspzincin metalloendopeptidase AsaP1.
FEBS Letters, 2016Co-Authors: Xenia Bogdanović, Gottfried J. Palm, Johanna Schwenteit, Rajesh Kumar Singh, B.k. Gudmundsdottir, Winfried HinrichsAbstract:The Gram-negative bacterium Aeromonas salmonicida is a fish pathogen for various fish species worldwide. Aeromonas salmonicida subsp. achromogenes produces the extracellular, toxic zinc endopeptidase AsaP1. Crystal structure analyses at 2.0 A resolution of two proteolytically inactive AsaP1 variants show the polypeptide folding of the protease domain and the propeptide domain. These first crystal structure analyses of a precursor of a Deuterolysin-like aspzincin protease provide insights into propeptide function, and specific substrate binding. A lysine side chain of the propeptide binds in the hydrophobic S1'-pocket interacting with three carboxylate side chains. An AsaP1 variant with a lysine to alanine exchange identifies the chaperone function of the propeptide.
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structural evidence of intramolecular propeptide inhibition of the aspzincin metalloendopeptidase asap1
FEBS Letters, 2016Co-Authors: Gottfried J. Palm, Johanna Schwenteit, Rajesh Kumar Singh, B.k. Gudmundsdottir, Xenia Bogdanovic, Winfried HinrichsAbstract:The Gram-negative bacterium Aeromonas salmonicida is a fish pathogen for various fish species worldwide. Aeromonas salmonicida subsp. achromogenes produces the extracellular, toxic zinc-endopeptidase AsaP1. Crystal structure analyses at 2.0 A resolution of two proteolytically inactive AsaP1 variants show the polypeptide folding of the protease domain and the propeptide domain. These first crystal structure analyses of a precursor of a Deuterolysin-like aspzincin protease provide insights in propeptide function, and specific substrate binding. A lysine side-chain of the propeptide binds in the hydrophobic S1′-pocket interacting with three carboxylate side-chains. An AsaP1 variant with a lysine to alanine exchange identifies the chaperone function of the propeptide. This article is protected by copyright. All rights reserved.
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the asap1 peptidase of aeromonas salmonicida subsp achromogenes is a highly conserved Deuterolysin metalloprotease family m35 and a major virulence factor
Journal of Bacteriology, 2009Co-Authors: Helga Arnadottir, Iris Hvanndal, Valgerdur Andresdottir, Sarah E Burr, Joachim Frey, B.k. GudmundsdottirAbstract:Infections by the bacterium Aeromonas salmonicida subsp. achromogenes cause significant disease in a number of fish species. In this study, we showed that AsaP1, a toxic 19-kDa metallopeptidase produced by A. salmonicida subsp. achromogenes, belongs to the group of extracellular peptidases (Aeromonas type) (MEROPS ID M35.003) of the Deuterolysin family of zinc-dependent aspzincin endopeptidases. The structural gene of AsaP1 was sequenced and found to be highly conserved among gram-negative bacteria. An isogenic ΔasaP1 A. salmonicida subsp. achromogenes strain was constructed, and its ability to infect fish was compared with that of the wild-type (wt) strain. The ΔasaP1 strain was found to infect Arctic charr, Atlantic salmon, and Atlantic cod, but its virulence was decreased relative to that of the wt strain. The 50% lethal dose of the AsaP1 mutant was 10-fold higher in charr and 5-fold higher in salmon than that of the wt strain. The pathology induced by the AsaP1-deficient strain was also different from that of the wt strain. Furthermore, the mutant established significant bacterial colonization in all observed organs without any signs of a host response in the infected tissue. AsaP1 is therefore the first member of the M35 family that has been shown to be a bacterial virulence factor.
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The AsaP1 Peptidase of Aeromonas salmonicida subsp. achromogenes Is a Highly Conserved Deuterolysin Metalloprotease (Family M35) and a Major Virulence Factor
Journal of Bacteriology, 2008Co-Authors: Helga Arnadottir, Iris Hvanndal, Valgerdur Andresdottir, Sarah E Burr, Joachim Frey, B.k. GudmundsdottirAbstract:Infections by the bacterium Aeromonas salmonicida subsp. achromogenes cause significant disease in a number of fish species. In this study, we showed that AsaP1, a toxic 19-kDa metallopeptidase produced by A. salmonicida subsp. achromogenes, belongs to the group of extracellular peptidases (Aeromonas type) (MEROPS ID M35.003) of the Deuterolysin family of zinc-dependent aspzincin endopeptidases. The structural gene of AsaP1 was sequenced and found to be highly conserved among gram-negative bacteria. An isogenic Delta asaP1 A. salmonicida subsp. achromogenes strain was constructed, and its ability to infect fish was compared with that of the wild-type (wt) strain. The Delta asaP1 strain was found to infect Arctic charr, Atlantic salmon, and Atlantic cod, but its virulence was decreased relative to that of the wt strain. The 50% lethal dose of the AsaP1 mutant was 10-fold higher in charr and 5-fold higher in salmon than that of the wt strain. The pathology induced by the AsaP1-deficient strain was also different from that of the wt strain. Furthermore, the mutant established significant bacterial colonization in all observed organs without any signs of a host response in the infected tissue. AsaP1 is therefore the first member of the M35 family that has been shown to be a bacterial virulence factor.
Makoto Sasaki - One of the best experts on this subject based on the ideXlab platform.
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Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study
Clinical and Translational Gastroenterology, 2018Co-Authors: Hiroki Ido, Hirotaka Matsubara, Manabu Kuroda, Akiko Takahashi, Yuzo Kojima, Satoshi Koikeda, Makoto SasakiAbstract:Introduction Recently, the population of individuals with non-celiac gluten sensitivity (NCGS) who do not have celiac disease but show improved symptoms with a gluten-free diet, has increased. Enzyme replacement therapy using digestive enzymes is expected to improve the symptoms of NCGS and be sustainable, since gluten-related proteins that are indigestible by the digestive system have been considered triggers of NCGS. Methods We selected patients with NCGS by screening demographic interviews, as well as performing medical evaluations, anti-gluten antibody tests, and gluten challenge tests. We performed a single-blind and crossover clinical trial with these subjects using a gluten challenge with the enzyme mixture or a placebo. Our designed enzyme mixture contained peptidase, semi alkaline protease, Deuterolysin, and cysteine protease derived from Aspergillus oryzae , Aspergillus melleus , Penicillium citrinum , and Carica papaya L., respectively. Results Administration of the enzyme mixture significantly decreased the change in the score of the symptom questionnaire before and after the gluten challenge compared with administration of the placebo in patients with NCGS without adverse events. In particular, the changes in the score of the gluten-induced incomplete evacuation feeling and headaches were significantly improved. The serum levels of interleukin (IL)-8, tumor necrosis factor (TNF)-α, andregulated on activation, normal T cell expressed and secreted (RANTES) in subjects were not significantly changed by gluten, as expected from previous studies, and the enzyme mixture did not affect these inflammatory markers. Conclusion In this human clinical study, we demonstrated the efficacy of the enzyme mixture derived from microorganisms and papaya in improving the symptoms of NCGS.
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Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study
Clinical and Translational Gastroenterology, 2018Co-Authors: Hiroki Ido, Hirotaka Matsubara, Manabu Kuroda, Akiko Takahashi, Yuzo Kojima, Satoshi Koikeda, Makoto SasakiAbstract:Recently, the population of individuals with non-celiac gluten sensitivity (NCGS) who do not have celiac disease but show improved symptoms with a gluten-free diet, has increased. Enzyme replacement therapy using digestive enzymes is expected to improve the symptoms of NCGS and be sustainable, since gluten-related proteins that are indigestible by the digestive system have been considered triggers of NCGS. We selected patients with NCGS by screening demographic interviews, as well as performing medical evaluations, anti-gluten antibody tests, and gluten challenge tests. We performed a single-blind and crossover clinical trial with these subjects using a gluten challenge with the enzyme mixture or a placebo. Our designed enzyme mixture contained peptidase, semi alkaline protease, Deuterolysin, and cysteine protease derived from Aspergillus oryzae, Aspergillus melleus, Penicillium citrinum, and Carica papaya L., respectively. Administration of the enzyme mixture significantly decreased the change in the score of the symptom questionnaire before and after the gluten challenge compared with administration of the placebo in patients with NCGS without adverse events. In particular, the changes in the score of the gluten-induced incomplete evacuation feeling and headaches were significantly improved. The serum levels of interleukin (IL)-8, tumor necrosis factor (TNF)-α, andregulated on activation, normal T cell expressed and secreted (RANTES) in subjects were not significantly changed by gluten, as expected from previous studies, and the enzyme mixture did not affect these inflammatory markers. In this human clinical study, we demonstrated the efficacy of the enzyme mixture derived from microorganisms and papaya in improving the symptoms of NCGS.
Xenia Bogdanovic - One of the best experts on this subject based on the ideXlab platform.
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structural evidence of intramolecular propeptide inhibition of the aspzincin metalloendopeptidase asap1
FEBS Letters, 2016Co-Authors: Gottfried J. Palm, Johanna Schwenteit, Rajesh Kumar Singh, B.k. Gudmundsdottir, Xenia Bogdanovic, Winfried HinrichsAbstract:The Gram-negative bacterium Aeromonas salmonicida is a fish pathogen for various fish species worldwide. Aeromonas salmonicida subsp. achromogenes produces the extracellular, toxic zinc-endopeptidase AsaP1. Crystal structure analyses at 2.0 A resolution of two proteolytically inactive AsaP1 variants show the polypeptide folding of the protease domain and the propeptide domain. These first crystal structure analyses of a precursor of a Deuterolysin-like aspzincin protease provide insights in propeptide function, and specific substrate binding. A lysine side-chain of the propeptide binds in the hydrophobic S1′-pocket interacting with three carboxylate side-chains. An AsaP1 variant with a lysine to alanine exchange identifies the chaperone function of the propeptide. This article is protected by copyright. All rights reserved.
Winfried Hinrichs - One of the best experts on this subject based on the ideXlab platform.
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Structural evidence of intramolecular propeptide inhibition of the aspzincin metalloendopeptidase AsaP1.
FEBS Letters, 2016Co-Authors: Xenia Bogdanović, Gottfried J. Palm, Johanna Schwenteit, Rajesh Kumar Singh, B.k. Gudmundsdottir, Winfried HinrichsAbstract:The Gram-negative bacterium Aeromonas salmonicida is a fish pathogen for various fish species worldwide. Aeromonas salmonicida subsp. achromogenes produces the extracellular, toxic zinc endopeptidase AsaP1. Crystal structure analyses at 2.0 A resolution of two proteolytically inactive AsaP1 variants show the polypeptide folding of the protease domain and the propeptide domain. These first crystal structure analyses of a precursor of a Deuterolysin-like aspzincin protease provide insights into propeptide function, and specific substrate binding. A lysine side chain of the propeptide binds in the hydrophobic S1'-pocket interacting with three carboxylate side chains. An AsaP1 variant with a lysine to alanine exchange identifies the chaperone function of the propeptide.
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structural evidence of intramolecular propeptide inhibition of the aspzincin metalloendopeptidase asap1
FEBS Letters, 2016Co-Authors: Gottfried J. Palm, Johanna Schwenteit, Rajesh Kumar Singh, B.k. Gudmundsdottir, Xenia Bogdanovic, Winfried HinrichsAbstract:The Gram-negative bacterium Aeromonas salmonicida is a fish pathogen for various fish species worldwide. Aeromonas salmonicida subsp. achromogenes produces the extracellular, toxic zinc-endopeptidase AsaP1. Crystal structure analyses at 2.0 A resolution of two proteolytically inactive AsaP1 variants show the polypeptide folding of the protease domain and the propeptide domain. These first crystal structure analyses of a precursor of a Deuterolysin-like aspzincin protease provide insights in propeptide function, and specific substrate binding. A lysine side-chain of the propeptide binds in the hydrophobic S1′-pocket interacting with three carboxylate side-chains. An AsaP1 variant with a lysine to alanine exchange identifies the chaperone function of the propeptide. This article is protected by copyright. All rights reserved.
Hiroki Ido - One of the best experts on this subject based on the ideXlab platform.
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Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study
Clinical and Translational Gastroenterology, 2018Co-Authors: Hiroki Ido, Hirotaka Matsubara, Manabu Kuroda, Akiko Takahashi, Yuzo Kojima, Satoshi Koikeda, Makoto SasakiAbstract:Introduction Recently, the population of individuals with non-celiac gluten sensitivity (NCGS) who do not have celiac disease but show improved symptoms with a gluten-free diet, has increased. Enzyme replacement therapy using digestive enzymes is expected to improve the symptoms of NCGS and be sustainable, since gluten-related proteins that are indigestible by the digestive system have been considered triggers of NCGS. Methods We selected patients with NCGS by screening demographic interviews, as well as performing medical evaluations, anti-gluten antibody tests, and gluten challenge tests. We performed a single-blind and crossover clinical trial with these subjects using a gluten challenge with the enzyme mixture or a placebo. Our designed enzyme mixture contained peptidase, semi alkaline protease, Deuterolysin, and cysteine protease derived from Aspergillus oryzae , Aspergillus melleus , Penicillium citrinum , and Carica papaya L., respectively. Results Administration of the enzyme mixture significantly decreased the change in the score of the symptom questionnaire before and after the gluten challenge compared with administration of the placebo in patients with NCGS without adverse events. In particular, the changes in the score of the gluten-induced incomplete evacuation feeling and headaches were significantly improved. The serum levels of interleukin (IL)-8, tumor necrosis factor (TNF)-α, andregulated on activation, normal T cell expressed and secreted (RANTES) in subjects were not significantly changed by gluten, as expected from previous studies, and the enzyme mixture did not affect these inflammatory markers. Conclusion In this human clinical study, we demonstrated the efficacy of the enzyme mixture derived from microorganisms and papaya in improving the symptoms of NCGS.
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Combination of Gluten-Digesting Enzymes Improved Symptoms of Non-Celiac Gluten Sensitivity: A Randomized Single-blind, Placebo-controlled Crossover Study
Clinical and Translational Gastroenterology, 2018Co-Authors: Hiroki Ido, Hirotaka Matsubara, Manabu Kuroda, Akiko Takahashi, Yuzo Kojima, Satoshi Koikeda, Makoto SasakiAbstract:Recently, the population of individuals with non-celiac gluten sensitivity (NCGS) who do not have celiac disease but show improved symptoms with a gluten-free diet, has increased. Enzyme replacement therapy using digestive enzymes is expected to improve the symptoms of NCGS and be sustainable, since gluten-related proteins that are indigestible by the digestive system have been considered triggers of NCGS. We selected patients with NCGS by screening demographic interviews, as well as performing medical evaluations, anti-gluten antibody tests, and gluten challenge tests. We performed a single-blind and crossover clinical trial with these subjects using a gluten challenge with the enzyme mixture or a placebo. Our designed enzyme mixture contained peptidase, semi alkaline protease, Deuterolysin, and cysteine protease derived from Aspergillus oryzae, Aspergillus melleus, Penicillium citrinum, and Carica papaya L., respectively. Administration of the enzyme mixture significantly decreased the change in the score of the symptom questionnaire before and after the gluten challenge compared with administration of the placebo in patients with NCGS without adverse events. In particular, the changes in the score of the gluten-induced incomplete evacuation feeling and headaches were significantly improved. The serum levels of interleukin (IL)-8, tumor necrosis factor (TNF)-α, andregulated on activation, normal T cell expressed and secreted (RANTES) in subjects were not significantly changed by gluten, as expected from previous studies, and the enzyme mixture did not affect these inflammatory markers. In this human clinical study, we demonstrated the efficacy of the enzyme mixture derived from microorganisms and papaya in improving the symptoms of NCGS.