The Experts below are selected from a list of 29373 Experts worldwide ranked by ideXlab platform
Alberto Podjarny - One of the best experts on this subject based on the ideXlab platform.
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new insights into the enzymatic mechanism of human chitotriosidase chit1 catalytic domain by atomic resolution x ray diffraction and hybrid qm mm
Acta Crystallographica Section D-biological Crystallography, 2015Co-Authors: Firas Fadel, Yuguang Zhao, Raul E Cachau, A Cousidosiah, F X Ruiz, Karl Harlos, Eduardo Howard, Andre Mitschler, Alberto PodjarnyAbstract:Chitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N-acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in Immune-System Disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 A (PDB entry 1waw) to 0.95–1.10 A for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities.
Firas Fadel - One of the best experts on this subject based on the ideXlab platform.
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new insights into the enzymatic mechanism of human chitotriosidase chit1 catalytic domain by atomic resolution x ray diffraction and hybrid qm mm
Acta Crystallographica Section D-biological Crystallography, 2015Co-Authors: Firas Fadel, Yuguang Zhao, Raul E Cachau, A Cousidosiah, F X Ruiz, Karl Harlos, Eduardo Howard, Andre Mitschler, Alberto PodjarnyAbstract:Chitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N-acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in Immune-System Disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 A (PDB entry 1waw) to 0.95–1.10 A for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities.
Ridha Oueslati - One of the best experts on this subject based on the ideXlab platform.
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zearalenone induces immunotoxicity in mice possible protective effects of radish extract raphanus sativus
Journal of Pharmacy and Pharmacology, 2010Co-Authors: Jalila Ben Salahabbes, Samir Abbes, Zohra Houas, Mosaad A Abdelwahhab, Ridha OueslatiAbstract:Radish (Raphanus sativus) has been extensively studied for its preventive effects against different degenerative diseases. Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp and is frequently implicated in immunological Disorders and occasionally in hyperoestrogenic syndromes contributing to the increased risk of cancer and other diseases. The aims of this study were, firstly, to quantitatively evaluate the Tunisian radish extract (TRE) for its total flavonoids, isothiocyanates and antioxidant activity and, secondly, to investigate the protective role of TRE against Immune System Disorders in Balb/c mice treated with ZEN for two weeks. The results indicated that mice treated with ZEN (40 mg kg -1 ) alone showed a significant decrease in lymphocytes of the total white blood cells, immunoglobulin profile (IgG and IgM), B cells, T-cell sub-types (CD3 + , CD4 + and CD8 + ) and natural killer and pro-inflammatory cytokines. Mice treated with TRE (5, 10 or 15 mg kg -1 ) for 7 days before, during or after ZEN treatment, however, showed a significant improvement in lymphocyte, immunoglobulin profile, T-cell sub-types, B cells and pro-inflammatory cytokines. Moreover, treatment with the highest dose of TRE (15 mgkg -1 ) enhanced the release of tumour necrosis factor-a and interleukin-1/3 but the other parameters were comparable with those of the control. It could be concluded that TRE was effective in protecting against ZEN-induced immunological Disorders. These results supported our hypothesis that TRE contains several compounds that are able to prevent or inhibit ZEN toxicity.
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zearalenone induces immunotoxicity in mice possible protective effects of radish extract raphanus sativus
Journal of Pharmacy and Pharmacology, 2010Co-Authors: Jalila Ben Salahabbes, Samir Abbes, Zohra Houas, Mosaad A Abdelwahhab, Ridha OueslatiAbstract:Radish (Raphanus sativus) has been extensively studied for its preventive effects against different degenerative diseases. Zearalenone (ZEN) is a mycotoxin produced by Fusarium spp and is frequently implicated in immunological Disorders and occasionally in hyperoestrogenic syndromes contributing to the increased risk of cancer and other diseases. The aims of this study were, firstly, to quantitatively evaluate the Tunisian radish extract (TRE) for its total flavonoids, isothiocyanates and antioxidant activity and, secondly, to investigate the protective role of TRE against Immune System Disorders in Balb/c mice treated with ZEN for two weeks. The results indicated that mice treated with ZEN (40 mg kg(-1)) alone showed a significant decrease in lymphocytes of the total white blood cells, immunoglobulin profile (IgG and IgM), B cells, T-cell sub-types (CD3+, CD4+ and CD8+) and natural killer and pro-inflammatory cytokines. Mice treated with TRE (5, 10 or 15 mg kg(-1)) for 7 days before, during or after ZEN treatment, however, showed a significant improvement in lymphocyte, immunoglobulin profile, T-cell sub-types, B cells and pro-inflammatory cytokines. Moreover, treatment with the highest dose of TRE (15 mgkg(-1)) enhanced the release of tumour necrosis factor-alpha and interleukin-1beta but the other parameters were comparable with those of the control. It could be concluded that TRE was effective in protecting against ZEN-induced immunological Disorders. These results supported our hypothesis that TRE contains several compounds that are able to prevent or inhibit ZEN toxicity.
Andre Mitschler - One of the best experts on this subject based on the ideXlab platform.
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new insights into the enzymatic mechanism of human chitotriosidase chit1 catalytic domain by atomic resolution x ray diffraction and hybrid qm mm
Acta Crystallographica Section D-biological Crystallography, 2015Co-Authors: Firas Fadel, Yuguang Zhao, Raul E Cachau, A Cousidosiah, F X Ruiz, Karl Harlos, Eduardo Howard, Andre Mitschler, Alberto PodjarnyAbstract:Chitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N-acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in Immune-System Disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 A (PDB entry 1waw) to 0.95–1.10 A for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities.
Eduardo Howard - One of the best experts on this subject based on the ideXlab platform.
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new insights into the enzymatic mechanism of human chitotriosidase chit1 catalytic domain by atomic resolution x ray diffraction and hybrid qm mm
Acta Crystallographica Section D-biological Crystallography, 2015Co-Authors: Firas Fadel, Yuguang Zhao, Raul E Cachau, A Cousidosiah, F X Ruiz, Karl Harlos, Eduardo Howard, Andre Mitschler, Alberto PodjarnyAbstract:Chitotriosidase (CHIT1) is a human chitinase belonging to the highly conserved glycosyl hydrolase family 18 (GH18). GH18 enzymes hydrolyze chitin, an N-acetylglucosamine polymer synthesized by lower organisms for structural purposes. Recently, CHIT1 has attracted attention owing to its upregulation in Immune-System Disorders and as a marker of Gaucher disease. The 39 kDa catalytic domain shows a conserved cluster of three acidic residues, Glu140, Asp138 and Asp136, involved in the hydrolysis reaction. Under an excess concentration of substrate, CHIT1 and other homologues perform an additional activity, transglycosylation. To understand the catalytic mechanism of GH18 chitinases and the dual enzymatic activity, the structure and mechanism of CHIT1 were analyzed in detail. The resolution of the crystals of the catalytic domain was improved from 1.65 A (PDB entry 1waw) to 0.95–1.10 A for the apo and pseudo-apo forms and the complex with chitobiose, allowing the determination of the protonation states within the active site. This information was extended by hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. The results suggest a new mechanism involving changes in the conformation and protonation state of the catalytic triad, as well as a new role for Tyr27, providing new insights into the hydrolysis and transglycosylation activities.
