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evolution
amino acid sequences of NADH-preferring PHBHs of putative PHBHs identified in currently available bacterial genomes, phylogenetic analysis, overview. The pyridine nucleotide coenzyme specificity of PHBH emerged through adaptive evolution, and the NADH-preferring enzymes are the older versions of PHBH. Structural comparison and distance tree analysis of group A flavoprotein monooxygenases indicates that a similar protein segment as being responsible for the pyridine nucleotide coenzyme specificity of PHBH is involved in determining the pyridine nucleotide coenzyme specificity of the other group A members. Evolutionary rate calculation. Among the actinobacterial sequences presently available, most comprise the NADH-preferring fingerprint. However, Mycobacteria have a mixed type motif, often the first or both arginine(s) of the NADH-fingerprint are present but the remaining part is lacking. In addition, many mycobacterial sequences have parts of the NADPH-preferring fingerprint, especially, x(D/E)YVL(G/S)R
evolution
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evolutionary relationship between the NAD(P)H-dependent FAD-containing 4-hydroxybenzoate hydroxylases and phylogenetic analysis of group A FPMOs, overview
evolution
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phylogenetic analysis shows that FAD-dependent 4-hydroxybenzoate hydroxylases reside in distinct clades of the group A flavoprotein monooxygenase (FPMO) family, indicating their separate divergence from a common ancestor. Protein homology modeling reveals that the fungal 4-hydroxybenzoate 3-hydroxylase PhhA is structurally related to phenol hydroxylase (PHHY) and 3-hydroxybenzoate 4-hydroxylase (3HB4H). 4-Hydroxybenzoate 1-hydroxylase (4HB1H) from yeast catalyzes an oxidative decarboxylation reaction and is structurally similar to 3-hydroxybenzoate 6-hydroxylase (3HB6H), salicylate hydroxylase (SALH) and 6-hydroxynicotinate 3-monooxygenase (6HNMO). Group A FPMOs are involved in the aerobic microbial catabolism of 4-hydroxybenzoate. Phylogenetic analysis and structure comparisons, detailed overview
evolution
the PobA enzyme structure is highly conserved across various organisms. Active-site residues Tyr201, Ser212, Arg214, Tyr222 and Pro293 interact with the carboxyl and phenolic components of 4-HB and are essential for its oxidative catalysis
evolution
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the PobA enzyme structure is highly conserved across various organisms. Active-site residues Tyr201, Ser212, Arg214, Tyr222 and Pro293 interact with the carboxyl and phenolic components of 4-HB and are essential for its oxidative catalysis
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evolution
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evolutionary relationship between the NAD(P)H-dependent FAD-containing 4-hydroxybenzoate hydroxylases and phylogenetic analysis of group A FPMOs, overview
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evolution
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phylogenetic analysis shows that FAD-dependent 4-hydroxybenzoate hydroxylases reside in distinct clades of the group A flavoprotein monooxygenase (FPMO) family, indicating their separate divergence from a common ancestor. Protein homology modeling reveals that the fungal 4-hydroxybenzoate 3-hydroxylase PhhA is structurally related to phenol hydroxylase (PHHY) and 3-hydroxybenzoate 4-hydroxylase (3HB4H). 4-Hydroxybenzoate 1-hydroxylase (4HB1H) from yeast catalyzes an oxidative decarboxylation reaction and is structurally similar to 3-hydroxybenzoate 6-hydroxylase (3HB6H), salicylate hydroxylase (SALH) and 6-hydroxynicotinate 3-monooxygenase (6HNMO). Group A FPMOs are involved in the aerobic microbial catabolism of 4-hydroxybenzoate. Phylogenetic analysis and structure comparisons, detailed overview
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malfunction
replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
malfunction
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replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
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malfunction
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replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
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malfunction
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replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
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malfunction
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replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
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malfunction
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replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
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malfunction
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replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
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malfunction
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replacement of Tyr385 with Phe forms a mutant, which enables the production of 3,4,5-trihydroxybenzonate (gallic acid) from 3,4-DOHB, although the catalytic activity of the mutant is quite low. The L199V/Y385F double mutant exhibits activity for producing gallic acid 4.3fold higher than that of the Y385F single mutant. This improvement in catalytic activity is primarily due to the suppression of a shunt reaction that wasts NADPH by producing H2O2, molecular mechanism underlying this higher catalytic activity, molecular dynamics simulations and quantum mechanics/molecular mechanics calculations, overview
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metabolism
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enzyme PHBH is almost exclusively found in prokaryotes, where its induction, usually as a consequence of lignin degradation, results in the regioselective formation of protocatechuate, one of the central intermediates in the global carbon cycle
metabolism
the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
metabolism
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the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
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metabolism
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the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
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metabolism
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the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
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metabolism
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the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
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metabolism
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the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
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metabolism
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the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
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metabolism
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enzyme PHBH is almost exclusively found in prokaryotes, where its induction, usually as a consequence of lignin degradation, results in the regioselective formation of protocatechuate, one of the central intermediates in the global carbon cycle
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metabolism
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the NADPH-dependent 4-HBA hydroxylase from Pseudomonas aeruginosa (Pa PobA) natively catalyzes the first step in gallic acid biosynthesis
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physiological function
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the pobA gene encoding the 4-hydroxybenzoate 3-monooxygenase is expressed during growth on hydroxybenzoic acids and glucose
physiological function
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4-hydroxybenzoate (4-HB) is a common intermediate in lignin degradation. It is one of the aromatic acids that arise from the Calpha-Cbeta cleavage of lignin components. In aerobic bacteria, 4-HB usually is converted to the ring-fission substrate 3,4-dihydroxybenzoate (protocatechuate, PCA). This reaction is catalyzed by the NAD(P)H-dependent flavoprotein monooxygenase (FPMO) 4-hydroxybenzoate 3-hydroxylase (PHBH)
physiological function
PobA is a flavin-dependent monooxygenase that utilizes one O atom from O2 to hydroxylate 4-hydroxybenzoate, while reducing the other O atom to water
physiological function
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PobA is a flavin-dependent monooxygenase that utilizes one O atom from O2 to hydroxylate 4-hydroxybenzoate, while reducing the other O atom to water
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physiological function
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4-hydroxybenzoate (4-HB) is a common intermediate in lignin degradation. It is one of the aromatic acids that arise from the Calpha-Cbeta cleavage of lignin components. In aerobic bacteria, 4-HB usually is converted to the ring-fission substrate 3,4-dihydroxybenzoate (protocatechuate, PCA). This reaction is catalyzed by the NAD(P)H-dependent flavoprotein monooxygenase (FPMO) 4-hydroxybenzoate 3-hydroxylase (PHBH)
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additional information
energy profiling from enzyme protein structure is realized by means of a coarse-grained residue-level pair potential function modeling, overview
additional information
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enzyme protein homology modeling of An_PhhA using the structure file of Tc_PHHY (PDB ID 1pn0) as template, overview. Hydroxylase enzymes structure comparisons, overview
additional information
in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
additional information
sequence comparisons, three-dimensional enzyme structure analysis, and structure comparisons with 2-hydroxybiphenyl 3-monooxygenase (HbpA) from Pseudomonas nitroreducens and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase (MHPCO) from Mesorhizobium japonicum, overview. Despite having only 14% similarity in their primary sequences, pairwise structure alignments of PobA from Pseudomonas putida with HbpA from Pseudomonas nitroreducens and MHPCO from Mesorhizobium japonicum reveal local similarities between these structures. Key residues in the FAD-binding and substrate-binding sites of PobA are highly conserved spatially across the proteins from all three species. The PobA from Pseudomonas putida is structurally very similar to PobA from Pseudomonas fluorescens and from Pseudomonas aeruginosa. Key secondary-structure elements important for catalysis, such as the betaalphabeta fold, beta-sheet wall and alpha12 helix, are conserved across this expanded class of oxygenases
additional information
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sequence comparisons, three-dimensional enzyme structure analysis, and structure comparisons with 2-hydroxybiphenyl 3-monooxygenase (HbpA) from Pseudomonas nitroreducens and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase (MHPCO) from Mesorhizobium japonicum, overview. Despite having only 14% similarity in their primary sequences, pairwise structure alignments of PobA from Pseudomonas putida with HbpA from Pseudomonas nitroreducens and MHPCO from Mesorhizobium japonicum reveal local similarities between these structures. Key residues in the FAD-binding and substrate-binding sites of PobA are highly conserved spatially across the proteins from all three species. The PobA from Pseudomonas putida is structurally very similar to PobA from Pseudomonas fluorescens and from Pseudomonas aeruginosa. Key secondary-structure elements important for catalysis, such as the betaalphabeta fold, beta-sheet wall and alpha12 helix, are conserved across this expanded class of oxygenases
additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
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additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
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additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
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additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
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additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
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additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
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additional information
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sequence comparisons, three-dimensional enzyme structure analysis, and structure comparisons with 2-hydroxybiphenyl 3-monooxygenase (HbpA) from Pseudomonas nitroreducens and 2-methyl-3-hydroxypyridine-5-carboxylic acid oxygenase (MHPCO) from Mesorhizobium japonicum, overview. Despite having only 14% similarity in their primary sequences, pairwise structure alignments of PobA from Pseudomonas putida with HbpA from Pseudomonas nitroreducens and MHPCO from Mesorhizobium japonicum reveal local similarities between these structures. Key residues in the FAD-binding and substrate-binding sites of PobA are highly conserved spatially across the proteins from all three species. The PobA from Pseudomonas putida is structurally very similar to PobA from Pseudomonas fluorescens and from Pseudomonas aeruginosa. Key secondary-structure elements important for catalysis, such as the betaalphabeta fold, beta-sheet wall and alpha12 helix, are conserved across this expanded class of oxygenases
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additional information
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enzyme protein homology modeling of An_PhhA using the structure file of Tc_PHHY (PDB ID 1pn0) as template, overview. Hydroxylase enzymes structure comparisons, overview
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additional information
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in wild-type PobA structure (PDB ID 1IUW), the productive binding mode is described by the hydrogen-bonding networks stabilizing 4-HBA and positioning the 3-carbon toward FAD for hydroxylation, comparison with enzyme mutants Da015 and DA016
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