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Volker Ullrich - One of the best experts on this subject based on the ideXlab platform.
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PEROXYNITRITE INACTIVATES PROSTACYCLIN SYNTHASE BY HEME–THIOLATE-CATALYZED TYROSINE NITRATION
Drug metabolism reviews, 1999Co-Authors: Ming-hui Zou, Akin Yesilkaya, Volker UllrichAbstract:Previous work has shown a sensitive inhibition of prostacyclin synthase activity by peroxynitrite as well as by superoxide in the presence of NO donors. Neither superoxide nor NO alone nor decomposed peroxynitrite is effective. The inhibition of activity was paralleled by a nitration of a tyrosine residue and both could be prevented by a stable Substrate Analog. The same IC50 value for peroxynitrite was also found for the cellular prostacyclin activity in endothelial and kidney mesangial cells, indicating that the antioxidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine staining after treatment of the tissue with 1 μM peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.
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peroxynitrite inactivates prostacyclin synthase by heme thiolate catalyzed tyrosine nitration
Drug Metabolism Reviews, 1999Co-Authors: Ming-hui Zou, Akin Yesilkaya, Volker UllrichAbstract:Previous work has shown a sensitive inhibition of prostacyclin synthase activity by peroxynitrite as well as by superoxide in the presence of NO donors. Neither superoxide nor NO alone nor decomposed peroxynitrite is effective. The inhibition of activity was paralleled by a nitration of a tyrosine residue and both could be prevented by a stable Substrate Analog. The same IC50 value for peroxynitrite was also found for the cellular prostacyclin activity in endothelial and kidney mesangial cells, indicating that the antioxidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine staining after treatment of the tissue with 1 μM peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.
Ming-hui Zou - One of the best experts on this subject based on the ideXlab platform.
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PEROXYNITRITE INACTIVATES PROSTACYCLIN SYNTHASE BY HEME–THIOLATE-CATALYZED TYROSINE NITRATION
Drug metabolism reviews, 1999Co-Authors: Ming-hui Zou, Akin Yesilkaya, Volker UllrichAbstract:Previous work has shown a sensitive inhibition of prostacyclin synthase activity by peroxynitrite as well as by superoxide in the presence of NO donors. Neither superoxide nor NO alone nor decomposed peroxynitrite is effective. The inhibition of activity was paralleled by a nitration of a tyrosine residue and both could be prevented by a stable Substrate Analog. The same IC50 value for peroxynitrite was also found for the cellular prostacyclin activity in endothelial and kidney mesangial cells, indicating that the antioxidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine staining after treatment of the tissue with 1 μM peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.
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peroxynitrite inactivates prostacyclin synthase by heme thiolate catalyzed tyrosine nitration
Drug Metabolism Reviews, 1999Co-Authors: Ming-hui Zou, Akin Yesilkaya, Volker UllrichAbstract:Previous work has shown a sensitive inhibition of prostacyclin synthase activity by peroxynitrite as well as by superoxide in the presence of NO donors. Neither superoxide nor NO alone nor decomposed peroxynitrite is effective. The inhibition of activity was paralleled by a nitration of a tyrosine residue and both could be prevented by a stable Substrate Analog. The same IC50 value for peroxynitrite was also found for the cellular prostacyclin activity in endothelial and kidney mesangial cells, indicating that the antioxidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine staining after treatment of the tissue with 1 μM peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.
I P Kuranova - One of the best experts on this subject based on the ideXlab platform.
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structure of the carboxypeptidase b complex with n sulfamoyl l phenylalanine a transition state Analog of non specific Substrate
Journal of Biomolecular Structure & Dynamics, 2018Co-Authors: Valery Kh Akparov, V I Timofeev, Ilyas G Khaliullin, V K Svedas, I P KuranovaAbstract:Carboxypeptidase B (EC 3.4.17.2) (CPB) is commonly used in the industrial insulin production and as a template for drug design. However, its ability to discriminate Substrates with hydrophobic, hydrophilic, and charged side chains is not well understood. We report structure of CPB complex with a transition state Analog N-sulfamoyl-L-phenylalanine solved at 1.74A. The study provided an insight into structural basis of CPB Substrate specificity. Ligand binding is affected by structure-depended conformational changes of Asp255 in S1’-subsite, interactions with Asn144 and Arg145 in C-terminal binding subsite, and Glu270 in the catalytic center. Side chain of the non-specific Substrate Analog SPhe in comparison with that of specific Substrate Analog SArg (reported earlier) not only loses favorable electrostatic interactions and two hydrogen bonds with Asp255 and three fixed water molecules, but is forced to be in the unfavorable hydrophilic environment. Thus, Ser207, Gly253, Tyr248, and Asp255 residues play ma...
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Structure of the carboxypeptidase B complex with N-sulfamoyl-L-phenylalanine – a transition state Analog of non-specific Substrate
Journal of biomolecular structure & dynamics, 2017Co-Authors: Valery Kh Akparov, V I Timofeev, Ilyas G Khaliullin, V K Svedas, I P KuranovaAbstract:Carboxypeptidase B (EC 3.4.17.2) (CPB) is commonly used in the industrial insulin production and as a template for drug design. However, its ability to discriminate Substrates with hydrophobic, hydrophilic, and charged side chains is not well understood. We report structure of CPB complex with a transition state Analog N-sulfamoyl-L-phenylalanine solved at 1.74A. The study provided an insight into structural basis of CPB Substrate specificity. Ligand binding is affected by structure-depended conformational changes of Asp255 in S1’-subsite, interactions with Asn144 and Arg145 in C-terminal binding subsite, and Glu270 in the catalytic center. Side chain of the non-specific Substrate Analog SPhe in comparison with that of specific Substrate Analog SArg (reported earlier) not only loses favorable electrostatic interactions and two hydrogen bonds with Asp255 and three fixed water molecules, but is forced to be in the unfavorable hydrophilic environment. Thus, Ser207, Gly253, Tyr248, and Asp255 residues play ma...
Akin Yesilkaya - One of the best experts on this subject based on the ideXlab platform.
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PEROXYNITRITE INACTIVATES PROSTACYCLIN SYNTHASE BY HEME–THIOLATE-CATALYZED TYROSINE NITRATION
Drug metabolism reviews, 1999Co-Authors: Ming-hui Zou, Akin Yesilkaya, Volker UllrichAbstract:Previous work has shown a sensitive inhibition of prostacyclin synthase activity by peroxynitrite as well as by superoxide in the presence of NO donors. Neither superoxide nor NO alone nor decomposed peroxynitrite is effective. The inhibition of activity was paralleled by a nitration of a tyrosine residue and both could be prevented by a stable Substrate Analog. The same IC50 value for peroxynitrite was also found for the cellular prostacyclin activity in endothelial and kidney mesangial cells, indicating that the antioxidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine staining after treatment of the tissue with 1 μM peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.
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peroxynitrite inactivates prostacyclin synthase by heme thiolate catalyzed tyrosine nitration
Drug Metabolism Reviews, 1999Co-Authors: Ming-hui Zou, Akin Yesilkaya, Volker UllrichAbstract:Previous work has shown a sensitive inhibition of prostacyclin synthase activity by peroxynitrite as well as by superoxide in the presence of NO donors. Neither superoxide nor NO alone nor decomposed peroxynitrite is effective. The inhibition of activity was paralleled by a nitration of a tyrosine residue and both could be prevented by a stable Substrate Analog. The same IC50 value for peroxynitrite was also found for the cellular prostacyclin activity in endothelial and kidney mesangial cells, indicating that the antioxidant potential of the cell cannot prevent the inactivation. Aortic tissue shows a co-localization of prostacyclin synthase and nitrotyrosine staining after treatment of the tissue with 1 μM peroxynitrite. It can be speculated that this pathway of enzyme nitration is of pathophysiological significance.
Nafsika H. Georgopapadakou - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of yeast inositol phosphorylceramide synthase by aureobasidin A measured by a fluorometric assay
FEBS letters, 1999Co-Authors: Wenyan Zhong, Dennis J. Murphy, Nafsika H. GeorgopapadakouAbstract:Inositol phosphorylceramide synthase (IPC synthase) is an essential and unique enzyme in fungal sphingolipid biosynthesis and is the target of the cyclic nonadepsipeptide antibiotic aureobasidin A. As a first step towards understanding the mechanism of aureobasidin A inhibition, we developed a fluorometric HPLC assay for IPC synthase using the Saccha- romyces cerevisiae enzyme and the fluorescent Substrate Analog 6-(N-(7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-hexanoyl ceram- ide (C6-NBD-cer). The kinetic parameters for C6-NBD-cer were comparable to those for the synthetic Substrate N-acetyl- sphinganine used previously. Aureobasidin A acted as a tight- binding, non-competitive inhibitor with respect to C6-NBD-cer and had a Ki of 0.55 nM. z 1999 Federation of European Biochemical Societies.
