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Kenji Aoki - One of the best experts on this subject based on the ideXlab platform.
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Constitutive Synthesis of Enzymes Involved in 2-Aminophenol Metabolism and Inducible Synthesis of Enzymes Involved in Benzoate, p-Hydroxybenzoate, and Protocatechuate Metabolism in Pseudomonas sp. Strain AP-3
Bioscience biotechnology and biochemistry, 2005Co-Authors: Shinji Takenaka, Shuichiro Murakami, Young-ju Kim, Endang Setyorini, Kenji AokiAbstract:Pseudomonas sp. strain AP-3 grows on benzoate, p-hydroxybenzoate, protocatechuate, and 2-Aminophenol as sole carbon and energy source. This strain converted benzoate and p-hydroxybenzoate to catechol and protocatechuate respectively, which were metabolized via the ortho-cleavage pathway. The enzymes responsible for these reactions were shown to be inducible. In contrast, strain AP-3 constitutively expresses the enzymes involved in the metabolism of 2-Aminophenol.
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Complete nucleotide sequence and functional analysis of the genes for 2-Aminophenol metabolism from Pseudomonas sp. AP-3.
Archives of microbiology, 2000Co-Authors: Shinji Takenaka, Shuichiro Murakami, Young-ju Kim, Kenji AokiAbstract:A 13.9-kb region, which contained the 2-Aminophenol 1,6-dioxygenase genes (amnBA) reported before, was cloned from the 2-Aminophenol-assimilating bacterium Pseudomonas sp. AP-3. The complete nucleotide sequence of this region was determined and six genes were found downstream of amnBA. The eight genes together were designated amnBACFEDHG. Each gene was similar to the corresponding gene operating in the meta-cleavage pathway, except for amnB, amnA, and amnD. The four 2-Aminophenol-metabolizing enzymes, 2-aminomuconic 6-semialdehyde dehydrogenase, 2-aminomuconate deaminase, 4-oxalocrotonate decarboxylase, and 2-oxopent-4-enoate hydratase, were purified and characterized. NH2-terminal amino acid sequences of each purified enzyme agreed with those deduced from amnC, amnF, amnE, and amnD, respectively. These genes were therefore assigned as the genes encoding these respective proteins. The tight clustering of the amn genes, which were all transcribed in the same direction, raised the possibility that these genes formed a single operon. The organization of the amn genes was entirely different from that of the atd, dmp, and xyl genes reported in the meta-cleavage pathway, although these latter genes clustered similarly.
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Metabolism of 2-Aminophenol by Pseudomonas sp. AP-3: modified meta-cleavage pathway.
Archives of microbiology, 1998Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kenji AokiAbstract:A novel pathway for 2-Aminophenol metabolism by Pseudomonas sp. AP-3 is proposed. The proposed pathway is similar to that known for meta-cleavage of catechol except that one of the hydroxyl groups on the metabolites is replaced by an amino group. During the degradation of 2-Aminophenol, 2-amino-2,4-pentadienoic acid is the last metabolite containing an amino group. We, therefore, propose a modified meta-cleavage pathway for the 2-Aminophenol metabolism.
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Novel genes encoding 2-Aminophenol 1,6-dioxygenase from Pseudomonas species AP-3 growing on 2-Aminophenol and catalytic properties of the purified enzyme.
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
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Novel Genes Encoding 2-Aminophenol 1,6-Dioxygenase fromPseudomonas Species AP-3 Growing on 2-Aminophenol and Catalytic Properties of the Purified Enzyme
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
Shinji Takenaka - One of the best experts on this subject based on the ideXlab platform.
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Constitutive Synthesis of Enzymes Involved in 2-Aminophenol Metabolism and Inducible Synthesis of Enzymes Involved in Benzoate, p-Hydroxybenzoate, and Protocatechuate Metabolism in Pseudomonas sp. Strain AP-3
Bioscience biotechnology and biochemistry, 2005Co-Authors: Shinji Takenaka, Shuichiro Murakami, Young-ju Kim, Endang Setyorini, Kenji AokiAbstract:Pseudomonas sp. strain AP-3 grows on benzoate, p-hydroxybenzoate, protocatechuate, and 2-Aminophenol as sole carbon and energy source. This strain converted benzoate and p-hydroxybenzoate to catechol and protocatechuate respectively, which were metabolized via the ortho-cleavage pathway. The enzymes responsible for these reactions were shown to be inducible. In contrast, strain AP-3 constitutively expresses the enzymes involved in the metabolism of 2-Aminophenol.
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Complete nucleotide sequence and functional analysis of the genes for 2-Aminophenol metabolism from Pseudomonas sp. AP-3.
Archives of microbiology, 2000Co-Authors: Shinji Takenaka, Shuichiro Murakami, Young-ju Kim, Kenji AokiAbstract:A 13.9-kb region, which contained the 2-Aminophenol 1,6-dioxygenase genes (amnBA) reported before, was cloned from the 2-Aminophenol-assimilating bacterium Pseudomonas sp. AP-3. The complete nucleotide sequence of this region was determined and six genes were found downstream of amnBA. The eight genes together were designated amnBACFEDHG. Each gene was similar to the corresponding gene operating in the meta-cleavage pathway, except for amnB, amnA, and amnD. The four 2-Aminophenol-metabolizing enzymes, 2-aminomuconic 6-semialdehyde dehydrogenase, 2-aminomuconate deaminase, 4-oxalocrotonate decarboxylase, and 2-oxopent-4-enoate hydratase, were purified and characterized. NH2-terminal amino acid sequences of each purified enzyme agreed with those deduced from amnC, amnF, amnE, and amnD, respectively. These genes were therefore assigned as the genes encoding these respective proteins. The tight clustering of the amn genes, which were all transcribed in the same direction, raised the possibility that these genes formed a single operon. The organization of the amn genes was entirely different from that of the atd, dmp, and xyl genes reported in the meta-cleavage pathway, although these latter genes clustered similarly.
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Metabolism of 2-Aminophenol by Pseudomonas sp. AP-3: modified meta-cleavage pathway.
Archives of microbiology, 1998Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kenji AokiAbstract:A novel pathway for 2-Aminophenol metabolism by Pseudomonas sp. AP-3 is proposed. The proposed pathway is similar to that known for meta-cleavage of catechol except that one of the hydroxyl groups on the metabolites is replaced by an amino group. During the degradation of 2-Aminophenol, 2-amino-2,4-pentadienoic acid is the last metabolite containing an amino group. We, therefore, propose a modified meta-cleavage pathway for the 2-Aminophenol metabolism.
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Novel genes encoding 2-Aminophenol 1,6-dioxygenase from Pseudomonas species AP-3 growing on 2-Aminophenol and catalytic properties of the purified enzyme.
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
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Novel Genes Encoding 2-Aminophenol 1,6-Dioxygenase fromPseudomonas Species AP-3 Growing on 2-Aminophenol and Catalytic Properties of the Purified Enzyme
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
Shuichiro Murakami - One of the best experts on this subject based on the ideXlab platform.
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Constitutive Synthesis of Enzymes Involved in 2-Aminophenol Metabolism and Inducible Synthesis of Enzymes Involved in Benzoate, p-Hydroxybenzoate, and Protocatechuate Metabolism in Pseudomonas sp. Strain AP-3
Bioscience biotechnology and biochemistry, 2005Co-Authors: Shinji Takenaka, Shuichiro Murakami, Young-ju Kim, Endang Setyorini, Kenji AokiAbstract:Pseudomonas sp. strain AP-3 grows on benzoate, p-hydroxybenzoate, protocatechuate, and 2-Aminophenol as sole carbon and energy source. This strain converted benzoate and p-hydroxybenzoate to catechol and protocatechuate respectively, which were metabolized via the ortho-cleavage pathway. The enzymes responsible for these reactions were shown to be inducible. In contrast, strain AP-3 constitutively expresses the enzymes involved in the metabolism of 2-Aminophenol.
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Complete nucleotide sequence and functional analysis of the genes for 2-Aminophenol metabolism from Pseudomonas sp. AP-3.
Archives of microbiology, 2000Co-Authors: Shinji Takenaka, Shuichiro Murakami, Young-ju Kim, Kenji AokiAbstract:A 13.9-kb region, which contained the 2-Aminophenol 1,6-dioxygenase genes (amnBA) reported before, was cloned from the 2-Aminophenol-assimilating bacterium Pseudomonas sp. AP-3. The complete nucleotide sequence of this region was determined and six genes were found downstream of amnBA. The eight genes together were designated amnBACFEDHG. Each gene was similar to the corresponding gene operating in the meta-cleavage pathway, except for amnB, amnA, and amnD. The four 2-Aminophenol-metabolizing enzymes, 2-aminomuconic 6-semialdehyde dehydrogenase, 2-aminomuconate deaminase, 4-oxalocrotonate decarboxylase, and 2-oxopent-4-enoate hydratase, were purified and characterized. NH2-terminal amino acid sequences of each purified enzyme agreed with those deduced from amnC, amnF, amnE, and amnD, respectively. These genes were therefore assigned as the genes encoding these respective proteins. The tight clustering of the amn genes, which were all transcribed in the same direction, raised the possibility that these genes formed a single operon. The organization of the amn genes was entirely different from that of the atd, dmp, and xyl genes reported in the meta-cleavage pathway, although these latter genes clustered similarly.
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Metabolism of 2-Aminophenol by Pseudomonas sp. AP-3: modified meta-cleavage pathway.
Archives of microbiology, 1998Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kenji AokiAbstract:A novel pathway for 2-Aminophenol metabolism by Pseudomonas sp. AP-3 is proposed. The proposed pathway is similar to that known for meta-cleavage of catechol except that one of the hydroxyl groups on the metabolites is replaced by an amino group. During the degradation of 2-Aminophenol, 2-amino-2,4-pentadienoic acid is the last metabolite containing an amino group. We, therefore, propose a modified meta-cleavage pathway for the 2-Aminophenol metabolism.
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Novel genes encoding 2-Aminophenol 1,6-dioxygenase from Pseudomonas species AP-3 growing on 2-Aminophenol and catalytic properties of the purified enzyme.
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
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Novel Genes Encoding 2-Aminophenol 1,6-Dioxygenase fromPseudomonas Species AP-3 Growing on 2-Aminophenol and Catalytic Properties of the Purified Enzyme
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
Ryu Shinke - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of 2-Aminophenol by Pseudomonas sp. AP-3: modified meta-cleavage pathway.
Archives of microbiology, 1998Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kenji AokiAbstract:A novel pathway for 2-Aminophenol metabolism by Pseudomonas sp. AP-3 is proposed. The proposed pathway is similar to that known for meta-cleavage of catechol except that one of the hydroxyl groups on the metabolites is replaced by an amino group. During the degradation of 2-Aminophenol, 2-amino-2,4-pentadienoic acid is the last metabolite containing an amino group. We, therefore, propose a modified meta-cleavage pathway for the 2-Aminophenol metabolism.
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Novel genes encoding 2-Aminophenol 1,6-dioxygenase from Pseudomonas species AP-3 growing on 2-Aminophenol and catalytic properties of the purified enzyme.
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
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Novel Genes Encoding 2-Aminophenol 1,6-Dioxygenase fromPseudomonas Species AP-3 Growing on 2-Aminophenol and Catalytic Properties of the Purified Enzyme
The Journal of biological chemistry, 1997Co-Authors: Shinji Takenaka, Shuichiro Murakami, Ryu Shinke, Kazuhisa Hatakeyama, Hideaki Yukawa, Kenji AokiAbstract:Abstract 2-Aminophenol 1,6-dioxygenase was purified from the cell extracts of Pseudomonas sp. AP-3 grown on 2-Aminophenol. The product from 2-Aminophenol by catalysis of the purified enzyme was identified as 2-aminomuconic 6-semialdehyde by gas chromatographic and mass spectrometric analyses. The molecular mass of the native enzyme was 140 kDa based on gel filtration. It was dissociated into molecular mass subunits of 32 (α-subunit) and 40 kDa (β-subunit) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating that the dioxygenase was a heterotetramer of α2β2. The genes coding for the α- and β-subunits of the enzyme were cloned and sequenced. Open reading frames of the genes (amnA and amnB) were 816 and 918 base pairs in length, respectively. The amino acid sequences predicted from the open reading frames of amnA andamnB corresponded to the NH2-terminal amino acid sequences of the α-subunit (AmnA) and β-subunit (AmnB), respectively. The deduced amino acid sequences of AmnB showed identities to some extent with HpaD (25.4%) and HpcB (24.4%) that are homoprotocatechuate 2,3-dioxygenases from Escherichia coliW and C, respectively, belonging to class III in the extradiol dioxygenases. On the other hand, AmnA had identity (23.3%) with only AmnB among the enzymes examined.
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Partial purification and characterization of a bacterial dioxygenase that catalyzes the ring fission of 2-Aminophenol
Microbiological Research, 1997Co-Authors: Kenji Aoki, Shuichiro Murakami, S. Takenaka, Ryu ShinkeAbstract:Abstract A bacterial strain AP-3, grown on 2-Aminophenol as a sole carbon, nitrogen and energy source and isolated from soil, was identified as a Pseudomonas species. When Pseudomonas sp. AP-3 grew with this substrate, it synthesized an enzyme acting on 2-Aminophenol. This enzyme was purified with an 103-fold increase of the specific activity from its cell-free extracts. We proved that the purified enzyme was a dioxygenase catalyzing the ring fission between 1- and 6-positions of 2-Aminophenol with the consumption of 1 mol of O 2 per mol of substrate. The enzyme showed the maximal activity at pH 7.5. It was stable between pH 7.5 and 9 and up to 35°C. The molecular mass of this enzyme was 140 kDa by gel filtration.
Oleg I. Shadyro - One of the best experts on this subject based on the ideXlab platform.
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N-acyl derivatives of 4,6-di-tert-butyl-2-Aminophenol protect neutrophils from halogenating stress
Free Radical Biology and Medicine, 2018Co-Authors: Alena Kavalenka, G. N. Semenkova, Ivan Zholnerevich, G. A. Ksendzova, Victor L. Sorokin, Nadezda Amaegberi, Oleg I. ShadyroAbstract:Hypochlorous acid is an important microbicidal agent mainly formed by neutrophil myeloperoxidase (MPO), however HOCl hyperproduction leads to halogenating stress associated with different diseases. It is necessary to search for substances that can selectively prevent excessive HOCl generation. We synthesized a number of N-acyl derivatives of 4,6-di-tert-butyl-2-Aminophenol which exhibit antiradical activity in cell free model systems. The aim of the work is to study the effect of (N-(4,6-di-tert-butyl-2-Aminophenol)R, where R=-COCH3 (1), -COC2H5 (2), -COC3H7 (3) on ROS formation, secretory degranulation and viability of neutrophils exposed to HOCl. It has been shown that all compounds in micromolar concentrations reduce neutrophil ROS formation by 75% or more, inhibit MPO secretion and reduce HOCl production by MPO. It has been found that compounds 1–3 effectively intercept HOCl (up to 78%), but do not interact with H2O2. In concentrations of up to 1 μmol/l, compound 1 increases cell survival in the absence of exogenous HOCl, while compounds 2 and 3 do not influence it. Compound 1 in higher concentrations prevents destruction of neutrophils caused by addition of 300 μmol/l HOCl. Thus, compounds 1–3 can be considered as potential cytoprotectors under halogenating stress.
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INTRAMOLECULAR INTERACTIONS IN ANTIVIRAL DERIVATIVES OF 4,6-DI-tert-BUTYL-2-Aminophenol
Journal of Applied Spectroscopy, 2009Co-Authors: M. V. Belkov, G. A. Ksendzova, G. I. Polozov, I. V. Skornyakov, V. L. Sorokin, G. B. Tolstorozhev, Oleg I. ShadyroAbstract:We have used Fourier transform IR (FTIR) spectroscopy to study intramolecular interactions in solutions of 4,6-di-tert-butyl-2-Aminophenol in n-hexane. When the hydroxyl group in the molecule is ortho to the amino group, an O-H⋅⋅⋅N intramolecular hydrogen bond is formed in the 4-6-di-tert-butyl-2-Aminophenol derivatives, where the strength of the hydrogen bond depends on the type of substituent at the para position of the phenyl ring. If there are electron-donor groups on the phenyl ring, then a stronger O-H⋅⋅⋅N bond is formed in the 4,6-di-tert-butyl-2-Aminophenol derivatives than in molecules containing electron-acceptor Cl and Br atoms. Formation of the above-indicated intramolecular hydrogen bond affects the course of radiation-induced reac- tions occurring in n-hexane with participation of these compounds and also affects their antiviral activity. Introduction. The ability of viruses to acquire drug resistance is why it is necessary to develop effective new antiviral agents. Attempts have been made to create viral inhibitors with therapeutic action based on successive change in the interactions between the virus and the cell, accompanied by incorporation of anomalous nucleotides formed into the growing viral nucleic acid chain (1). But along with virus-inhibiting properties, these drugs have toxic effects due to possible action on the genetic apparatus of the "host cell". Accordingly, it is important to search for substances that can inhibit viral multiplication in stages unconnected with processes involving encoding and implementation of genetic information. Compounds able to control the prob- ability and direction of free-radical processes in biosystems may have such properties. Research in the field of free- radical virology has begun only recently, but already it has been shown that production of active forms of oxygen and activation of lipid peroxidation accompany the course of various viral infections, including rhinovirus, HIV, influenza, and various neuroviral infections, and chronic viral hepatitis infections (2). Therefore study of the possibility of using antioxidants for prophylaxis and treatment of viral diseases deserves attention in pharmacology. Some derivatives of Aminophenols (AP) having antioxidant properties have already found application as antivi- ral drugs for treatment of herpes infection (3-6). Steady-state radiolysis and IR spectroscopy have also been used to establish that the antioxidant properties of these Aminophenols are enhanced when there are hydroxyl groups in the free state in the molecules, and such properties are diminished when intramolecular hydrogen bonds of the type O-H⋅⋅⋅N or O-H⋅⋅⋅O=C are formed (7). Nevertheless, data available so far do not allow us to establish a clear connection between the effect of the substances on free-radical processes and their antiviral activity. Establishment of such dependences is complicated because of the unclear role of free-radical processes in development of viral pathology. Reactions with participation of activated forms of oxygen generally are nonselective, and such reactions can lead to damage to both the cells themselves and to the viruses incorporated within them. Therefore the unanswered question is what kind of substances, when introduced into biosystems, can change the direction of free-radical reactions to ensure preferable de- velopment of an antiviral effect.
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Synthesis and Antiviral Activity of N-Acyl Derivatives of 4,6-Di-( tert -butyl)-2-Aminophenol
Pharmaceutical Chemistry Journal, 2002Co-Authors: Oleg I. Shadyro, G. A. Ksendzova, G. I. Polozov, V. L. Sorokin, S. N. Nikolaeva, N. I. Pavlova, O. V. Savinova, E. I. BorekoAbstract:In recent years, the results of a number of experimental and clinical investigations have shown that antioxidants are promising candidates in the group of drugs used for the treatment of viral pathologies. The inhibiting action of antioxidants with respect to viral replication was reported for herpes simplex virus (HSV), hepatitis C, Epstein – Barr virus, cytomegalic inclusion virus, etc. [1]. It was also demonstrated that phenolic antioxidants of plant origin reduce HIV expression in tests on cell cultures [2]. In this context, we have undertaken the search for viral inhibitors among Aminophenol derivatives known to be capable of controlling the generation and utilization of free radicals [3]. Previously [4], we described the synthesis of N-acyl-substituted 4,6-di-tert-butyl-2-Aminophenols and reported on the results of pharmacological tests revealing sufficiently high anti-HSV activity in some of the synthesized compounds. In continuation of this search for new antiviral agents in the class of spatially constrained o-Aminophenol, we have synthesized a series of N-aryl and N-cycloalkyl derivatives of 4,6-di-tert-butyl-2-Aminophenol and tested these compounds for antiviral activity with respect to HSV and influenza species in cell cultures. The target compounds (I – VI) were synthesized by treating 3,5-di-tert-butylpyrocatechol with aniline, its derivatives, and cyclohexylamine in petroleum ether or methanol.
