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evolution
alcohol dehydrogenase is a fermentative enzyme that is highly conserved across species, from prokaryotes to fungi, plants, and animals
evolution
the class I type enzyme belongs to the medium-chain alcohol dehydrogenases, structural and evolutionary relationships of the pigeon enzyme, phylogenetic tree, overview
evolution
the class III type enzyme belongs to the medium-chain alcohol dehydrogenases, structural and evolutionary relationships of the dogfish enzyme, phylogenetic tree, overview
evolution
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the enzyme ADH3 belongs to the group III alcohol dehydrogenases
evolution
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the enzyme belongs to the short-chain alcohol dehydrogenases
evolution
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anti-Prelog NADH-dependent alcohol dehydrogenase enzymes are analysed for their specificity and activity on carbonyl substrates from different classes such as beta-ketoesters, aromatic ketones and aliphatic ketones. Acetobacter aceti ADH is highly active on beta-ketoesters such as methyl or ethyl 3-oxobutanoate, with maximum specific activity (66 U/mg) on ethyl 4-chloro-3-oxobutanoate. While the Acetobacter aceti, Aminobacter aminovorans and Gluconacetobacter diazotrophicus ADH enzymes are more specific for beta-ketoesters, the enzymes from Acetobacter senegalensis, Komagataeibacter xylinus, and Komagataeibacter medellinensis exhibit a broader substrate spectrum with moderate to high preference for acetophenone and its derivatives as well. ADH activity is favoured by the presence of electron-withdrawing halogen substituents F and Cl at para-position on the benzene ring of acetophenone, all the enzymes display significantly reduced activity with 4-bromoacetophenone and exhibit poor activity on the aliphatic substrate pentanone
evolution
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anti-Prelog NADH-dependent alcohol dehydrogenase enzymes are analysed for their specificity and activity on carbonyl substrates from different classes such as beta-ketoesters, aromatic ketones and aliphatic ketones. Acetobacter aceti ADH is highly active on beta-ketoesters such as methyl or ethyl 3-oxobutanoate, with maximum specific activity (66 U/mg) on ethyl 4-chloro-3-oxobutanoate. While the Acetobacter aceti, Aminobacter aminovorans and Gluconacetobacter diazotrophicus ADH enzymes are more specific for beta-ketoesters, the enzymes from Acetobacter senegalensis, Komagataeibacter xylinus, and Komagataeibacter medellinensis exhibit a broader substrate spectrum with moderate to high preference for acetophenone and its derivatives as well. ADH activity is favoured by the presence of electron-withdrawing halogen substituents F and Cl at para-position on the benzene ring of acetophenone, all the enzymes display significantly reduced activity with 4-bromoacetophenone and exhibit poor activity on the aliphatic substrate pentanone
evolution
anti-Prelog NADH-dependent alcohol dehydrogenase enzymes are analysed for their specificity and activity on carbonyl substrates from different classes such as beta-ketoesters, aromatic ketones and aliphatic ketones. Acetobacter aceti ADH is highly active on beta-ketoesters such as methyl or ethyl 3-oxobutanoate, with maximum specific activity (66 U/mg) on ethyl 4-chloro-3-oxobutanoate. While the Acetobacter aceti, Aminobacter aminovorans and Gluconacetobacter diazotrophicus ADH enzymes are more specific for beta-ketoesters, the enzymes from Acetobacter senegalensis, Komagataeibacter xylinus, and Komagataeibacter medellinensis exhibit a broader substrate spectrum with moderate to high preference for acetophenone and its derivatives as well. ADH activity is favoured by the presence of electron-withdrawing halogen substituents F and Cl at para-position on the benzene ring of acetophenone, all the enzymes display significantly reduced activity with 4-bromoacetophenone and exhibit poor activity on the aliphatic substrate pentanone
evolution
anti-Prelog NADH-dependent alcohol dehydrogenase enzymes are analysed for their specificity and activity on carbonyl substrates from different classes such as beta-ketoesters, aromatic ketones and aliphatic ketones. Acetobacter aceti ADH is highly active on beta-ketoesters such as methyl or ethyl 3-oxobutanoate, with maximum specific activity (66 U/mg) on ethyl 4-chloro-3-oxobutanoate. While the Acetobacter aceti, Aminobacter aminovorans and Gluconacetobacter diazotrophicus ADH enzymes are more specific for beta-ketoesters, the enzymes from Acetobacter senegalensis, Komagataeibacter xylinus, and Komagataeibacter medellinensis exhibit a broader substrate spectrum with moderate to high preference for acetophenone and its derivatives as well. ADH activity is favoured by the presence of electron-withdrawing halogen substituents F and Cl at para-position on the benzene ring of acetophenone, all the enzymes display significantly reduced activity with 4-bromoacetophenone and exhibit poor activity on the aliphatic substrate pentanone
evolution
anti-Prelog NADH-dependent alcohol dehydrogenase enzymes are analysed for their specificity and activity on carbonyl substrates from different classes such as beta-ketoesters, aromatic ketones and aliphatic ketones. Acetobacter aceti ADH is highly active on beta-ketoesters such as methyl or ethyl 3-oxobutanoate, with maximum specific activity (66 U/mg) on ethyl 4-chloro-3-oxobutanoate. While the Acetobacter aceti, Aminobacter aminovorans and Gluconacetobacter diazotrophicus ADH enzymes are more specific for beta-ketoesters, the enzymes from Acetobacter senegalensis, Komagataeibacter xylinus, and Komagataeibacter medellinensis exhibit a broader substrate spectrum with moderate to high preference for acetophenone and its derivatives as well. ADH activity is favoured by the presence of electron-withdrawing halogen substituents F and Cl at para-position on the benzene ring of acetophenone, all the enzymes display significantly reduced activity with 4-bromoacetophenone and exhibit poor activity on the aliphatic substrate pentanone
evolution
anti-Prelog NADH-dependent alcohol dehydrogenase enzymes are analysed for their specificity and activity on carbonyl substrates from different classes such as beta-ketoesters, aromatic ketones and aliphatic ketones. Acetobacter aceti ADH is highly active on beta-ketoesters such as methyl or ethyl 3-oxobutanoate, with maximum specific activity (66 U/mg) on ethyl 4-chloro-3-oxobutanoate. While the Acetobacter aceti, Aminobacter aminovorans, and Gluconacetobacter diazotrophicus ADH enzymes are more specific for beta-ketoesters, the enzymes from Acetobacter senegalensis, Komagataeibacter xylinus, and Komagataeibacter medellinensis exhibit a broader substrate spectrum with moderate to high preference for acetophenone and its derivatives as well. ADH activity is favoured by the presence of electron-withdrawing halogen substituents F and Cl at para-position on the benzene ring of acetophenone, all the enzymes display significantly reduced activity with 4-bromoacetophenone and exhibit poor activity on the aliphatic substrate pentanone
evolution
distribution of ADHE among the five eukaryotic supergroups, overview
evolution
the bifunctional AdhE enzyme is conserved in all bacterial kingdoms but also in more phylogenetically distant microorganisms such as green microalgae
evolution
the enzyme belongs to the quinone oxidoreductase (QOR) subfamily of the medium-chain dehydrogenase/reductase (MDR) family based on the results of amino acid sequence analysis and phylogenetic analysis
evolution
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anti-Prelog NADH-dependent alcohol dehydrogenase enzymes are analysed for their specificity and activity on carbonyl substrates from different classes such as beta-ketoesters, aromatic ketones and aliphatic ketones. Acetobacter aceti ADH is highly active on beta-ketoesters such as methyl or ethyl 3-oxobutanoate, with maximum specific activity (66 U/mg) on ethyl 4-chloro-3-oxobutanoate. While the Acetobacter aceti, Aminobacter aminovorans and Gluconacetobacter diazotrophicus ADH enzymes are more specific for beta-ketoesters, the enzymes from Acetobacter senegalensis, Komagataeibacter xylinus, and Komagataeibacter medellinensis exhibit a broader substrate spectrum with moderate to high preference for acetophenone and its derivatives as well. ADH activity is favoured by the presence of electron-withdrawing halogen substituents F and Cl at para-position on the benzene ring of acetophenone, all the enzymes display significantly reduced activity with 4-bromoacetophenone and exhibit poor activity on the aliphatic substrate pentanone
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evolution
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the enzyme belongs to the short-chain alcohol dehydrogenases
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evolution
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the enzyme ADH3 belongs to the group III alcohol dehydrogenases
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evolution
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the enzyme belongs to the quinone oxidoreductase (QOR) subfamily of the medium-chain dehydrogenase/reductase (MDR) family based on the results of amino acid sequence analysis and phylogenetic analysis
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evolution
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distribution of ADHE among the five eukaryotic supergroups, overview
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evolution
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alcohol dehydrogenase is a fermentative enzyme that is highly conserved across species, from prokaryotes to fungi, plants, and animals
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malfunction
methylglyoxal accumulation leads to G2-phase arrest by affecting cell growth, ROS production, viability, differentiation, and virulence. Phenotypes of enzyme-deficient cells, overview
malfunction
alternative binding modes in abortive NADH-alcohol complexes of horse liver alcohol dehydrogenase
malfunction
Arabidopsis suspension cell cultures show decreased ADH activity upon exposure to H2O2, but not to the thiol oxidizing agent diamide. Purified recombinant ADH shows a significant decrease in the enzyme activity by treatments with H2O2 and diethylamine NONOate (DEA/NO). Treatments leading to the formation of a disulfide bond between ADH and glutathione (protein S-glutathionylation) have no negative effect on the enzyme activity. LC-MS/MS analysis shows that Cys47 and Cys243 can make a stable disulfide bond with glutathione, suggesting redox sensitivity of these residues. Mutation of ADH Cys47 to Ser causes an almost complete loss of the enzyme activity while the Cys243 to Ser mutant have increased specific activity. Incubation of ADH with NAD+ or NADH prevents inhibition of the enzyme by H2O2 or DEA/NO. Binding of ADH with its cofactors may limit availability of Cys residues to redox modifications
malfunction
cells with increased ADHE abundance exhibit better survival under dark anoxia
malfunction
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cells with increased ADHE abundance exhibit better survival under dark anoxia
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metabolism
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enzyme is involved in phytol degradation
metabolism
ADHE can be involved either in ethanol production or assimilation, or both, depending upon environmental conditions
metabolism
the enzyme is involved in alginate metabolism
metabolism
anaerobic fermentative metabolism of glycerol. Proteome analysis as well as enzyme assays performed in cell-free extracts demonstrate that glycerol is degraded via glyceraldehyde-3-phosphate, which is further metabolized through the lower part of glycolysis leading to formation of mainly ethanol and hydrogen
metabolism
analysis of the anerobic metabolic routes involving the enzyme in Chlamydomonas reinhardtii, overview
metabolism
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analysis of the anerobic metabolic routes involving the enzyme in Chlamydomonas reinhardtii, overview
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physiological function
key enzyme in alcohol fermentation
physiological function
Adh1 is the primary alcohol dehydrogenase responsible for the production of ethanol from the reduction of acetaldehyde in Kluyveromyces marxianus
physiological function
deletion of the bifunctional alcohol and aldehyde dehydrogenase gene adhE reduces ethanol production by more than 95%. In the deletion strain, fermentation products shift from ethanol to lactate production and result in lower cell density and longer time to reach maximal cell density. It loses more than 85% of alcohol dehydrogenase activity. Aldehyde dehydrogenase activity does not appear to be affected, although its activity is low in cell extracts. Adding ubiquinone-0 to the aldehyde dehydrogenase assay increases activity in the parent strain but does not increase activity in the adhE deletion strain
physiological function
deletion of the bifunctional alcohol and aldehyde dehydrogenase gene adhE reduces ethanol production by more than 95%. In the deletion strains, fermentation products shift from ethanol to lactate production and result in lower cell density and longer time to reach maximal cell density. The deletion strain additionally contains a point mutation in the lactate dehydrogenase gene, which appears to deregulate its activation by fructose 1,6-bisphosphate, leading to constitutive activation of lactate dehydrogenase
physiological function
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different fermentation product yields observed in different ethanol-producing thernophiles that employ the phosphoroclastic pathway for pyruvate metabolism are related to the specific activities and the direction of specific oxidoreductases that control electron flow. Thermoanaerobium brockii extracts contain reversible NAD- and NADP-linked alcohol dehydrogenase activities that are not effectively inhibited by low NAD(P) or ethanol
physiological function
in ethanol-tolerant mutant strain, EA, the tolerant phenotype is primarily due to a mutated bifunctional acetaldehyde-CoA/alcohol dehydrogenase gene (adhE), with a complete loss of NADH-dependent activity and concomitant acquisition of NADPH-dependent activity, which likely affects electron flow in the mutant strain. Mutant adhE allele alone confers increased ethanol tolerance
physiological function
deletion of the Aadh1 gene affects growth of the cells with 1-butanol, ethanol and glucose as the carbon source, and a strain which overexpresses the gene metabolizes 1-butanol more rapidly. Aadh1 is a major enzyme for the synthesis of ethanol and the degradation of 1-butanol in Blastobotrys adeninivorans
physiological function
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acetaldehyde-alcohol dehydrogenase (ADHE) is a bifunctional enzyme consisting of two domains of an N-terminal acetaldehyde dehydrogenase (ALDH) and a C-terminal alcohol dehydrogenase (ADH). The N-terminal domain is responsible for the conversion of acetyl-CoA to acetaldehyde and the C-terminal domain is subsequently responsible for the conversion of acetaldehyde to ethanol. The enzyme is important in the cellular alcohol metabolism. The coenzyme A-acylating ADHE from Citrobacter sp. S-77 may play a pivotal role in modulating intracellular acetaldehyde concentration
physiological function
the enzyme catalyzes both methylglyoxal oxidation to pyruvate as well as its reduction to acetol. ADH1 activity likely shifts between methylglyoxal oxidation and reduction with a marked change in the intracellular redox state during the growth, such as GSH starvation. The enzyme is required for regulation of methylglyoxal content in the cell. Mgd activity is highly induced in GSH-deficient cells
physiological function
alcohol dehydrogenase (ADH) catalyzes the reversible conversion of acetaldehyde to ethanol while oxidizing NADH to NAD+. During hypoxia, it ensures the maintenance of the glycolytic flux by recycling NAD+ and controls toxic acetaldehyde produced by the decarboxylation of pyruvate. ADH catalyzes the last step of the ethanol fermentation pathway used by plants to cope with energy deficiency during hypoxic stress
physiological function
acetaldehyde-alcohol dehydrogenase (AdhE) enzymes are a key metabolic enzyme in bacterial physiology and pathogenicity. They convert acetyl-CoA to ethanol via an acetaldehyde intermediate during ethanol fermentation in an anaerobic environment. This two-step reaction is associated to NAD+ regeneration, essential for glycolysis. The biological role of AdhE seems to go beyond alcoholic fermentation. This protein could also be directly or indirectly involved in bacterial pathogenicity
physiological function
aldehyde/alcohol dehydrogenases (ADHEs) are bifunctional enzymes that commonly produce ethanol from acetyl-CoA with acetaldehyde as intermediate and play a key role in anaerobic redox balance in many fermenting bacteria. ADHEs are also present in photosynthetic unicellular eukaryotes
physiological function
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deletion of the bifunctional alcohol and aldehyde dehydrogenase gene adhE reduces ethanol production by more than 95%. In the deletion strains, fermentation products shift from ethanol to lactate production and result in lower cell density and longer time to reach maximal cell density. The deletion strain additionally contains a point mutation in the lactate dehydrogenase gene, which appears to deregulate its activation by fructose 1,6-bisphosphate, leading to constitutive activation of lactate dehydrogenase
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physiological function
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in ethanol-tolerant mutant strain, EA, the tolerant phenotype is primarily due to a mutated bifunctional acetaldehyde-CoA/alcohol dehydrogenase gene (adhE), with a complete loss of NADH-dependent activity and concomitant acquisition of NADPH-dependent activity, which likely affects electron flow in the mutant strain. Mutant adhE allele alone confers increased ethanol tolerance
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physiological function
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Adh1 is the primary alcohol dehydrogenase responsible for the production of ethanol from the reduction of acetaldehyde in Kluyveromyces marxianus
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physiological function
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deletion of the bifunctional alcohol and aldehyde dehydrogenase gene adhE reduces ethanol production by more than 95%. In the deletion strain, fermentation products shift from ethanol to lactate production and result in lower cell density and longer time to reach maximal cell density. It loses more than 85% of alcohol dehydrogenase activity. Aldehyde dehydrogenase activity does not appear to be affected, although its activity is low in cell extracts. Adding ubiquinone-0 to the aldehyde dehydrogenase assay increases activity in the parent strain but does not increase activity in the adhE deletion strain
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physiological function
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aldehyde/alcohol dehydrogenases (ADHEs) are bifunctional enzymes that commonly produce ethanol from acetyl-CoA with acetaldehyde as intermediate and play a key role in anaerobic redox balance in many fermenting bacteria. ADHEs are also present in photosynthetic unicellular eukaryotes
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physiological function
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key enzyme in alcohol fermentation
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additional information
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ADH1 molecular modeling and molecular dynamics simulations, and comparison to rat ADH5 enzyme, overview
additional information
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ADH5 molecular modeling and molecular dynamics simulations, and comparison to human ADH1 enzyme, overview
additional information
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the enzyme's two functional domains are fused into a single polypeptide by a linker amino acid region
additional information
docking studies suggest that the enzyme might have several active sites for different substrates, homology structure modeling, and detailed ligand molecular interaction analysis/molecular docking analysis using the template crystal structure with PDB ID 6C49, overview
additional information
high resolution X-ray crystallography of complexes with NADH and alcohols show alternative modes of binding in the active site. Enzyme crystallized with the good substrates NAD+ and 4-methylbenzyl alcohol is found to be an abortive complex of NADH with 4-methylbenzyl alcohol rotated to a non-productive mode as compared to the structures that resemble reactive Michaelis complexes with NAD+ and 2,2,2-trifluoroethanol or 2,3,4,5,6-pentafluorobenzyl alcohol. Crystals prepared with NAD+ and 4-bromobenzyl alcohol also form the abortive complex with NADH. Crystals prepared with NAD+ and the strong inhibitor 1H,1H-heptafluorobutanol also have NADH, and the alcohol is bound in two different conformations that illustrate binding flexibility. Oxidation of 2-methyl-2,4-pentanediol during the crystallization apparently leads to reduction of the NAD+. Kinetic studies show that high concentrations of alcohols can bind to the enzyme-NADH complex and activate or inhibit the enzyme. Models for the Michaelis complexes with NAD+-alcohol and NADH-aldehyde are proposed
additional information
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molecular dynamics simulations of enzyme-substrate interactions in the Michaelis complexes of wild-type ADH-A and Y294F/W295A double mutant. Interdependency between substrate/product and the cofactor in the ternary complex is determined, which directly affects the NADH dissociation rates, therefore, this substrate-coenzyme crosstalk plays a direct role in determining the turnover rates. Molecular dynamics of wild-type ADH-A (PDB ID 3jv7) and the A2 variant (PDB ID 5o8q) in complex with alcohols (R)- and (S)-4-phenyl-2-butanol
additional information
six Cys residues are found to be involved in the intrachain disulfide bond formation Cys99, Cys102, Cys105, Cys 113, Cys173, and Cys177. Among the six Cys residues, Cys99, Cys102, Cys105, and Cys 113 are bound to the same structural Zn atom, and Cys 177 is bound to the Zn atom at the catalytic center
additional information
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six Cys residues are found to be involved in the intrachain disulfide bond formation Cys99, Cys102, Cys105, Cys 113, Cys173, and Cys177. Among the six Cys residues, Cys99, Cys102, Cys105, and Cys 113 are bound to the same structural Zn atom, and Cys 177 is bound to the Zn atom at the catalytic center
additional information
filamentation of the bacterial bifunctional alcohol/aldehyde dehydrogenase AdhE is essential for substrate channeling and enzymatic regulation. Incubation with NAD+ and Fe2+ is sufficient to extend the filaments. The addition of coenzyme A does not impair the conformational change triggered by NAD+ and Fe2+. In the same conditions, NADH and Fe2+ are not able to trigger a conformational change from the compact to the extended form. Comparison of the structure of AdhE in its extended conformation with monofunctional ADH and AlDH enzymes, overview. The substrate/product channels of both the AlDH and ADH domains lead to the two cavities located at the AlDH-ADH interfaces within the AdhE dimer. The loops 2 and 3 seal this cavity by mediating the interactions between the AlDH and ADH domains. This allows a direct channeling between the AlDH and ADH domain active sites
additional information
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filamentation of the bacterial bifunctional alcohol/aldehyde dehydrogenase AdhE is essential for substrate channeling and enzymatic regulation. Incubation with NAD+ and Fe2+ is sufficient to extend the filaments. The addition of coenzyme A does not impair the conformational change triggered by NAD+ and Fe2+. In the same conditions, NADH and Fe2+ are not able to trigger a conformational change from the compact to the extended form. Comparison of the structure of AdhE in its extended conformation with monofunctional ADH and AlDH enzymes, overview. The substrate/product channels of both the AlDH and ADH domains lead to the two cavities located at the AlDH-ADH interfaces within the AdhE dimer. The loops 2 and 3 seal this cavity by mediating the interactions between the AlDH and ADH domains. This allows a direct channeling between the AlDH and ADH domain active sites
additional information
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molecular dynamics simulations of enzyme-substrate interactions in the Michaelis complexes of wild-type ADH-A and Y294F/W295A double mutant. Interdependency between substrate/product and the cofactor in the ternary complex is determined, which directly affects the NADH dissociation rates, therefore, this substrate-coenzyme crosstalk plays a direct role in determining the turnover rates. Molecular dynamics of wild-type ADH-A (PDB ID 3jv7) and the A2 variant (PDB ID 5o8q) in complex with alcohols (R)- and (S)-4-phenyl-2-butanol
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additional information
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docking studies suggest that the enzyme might have several active sites for different substrates, homology structure modeling, and detailed ligand molecular interaction analysis/molecular docking analysis using the template crystal structure with PDB ID 6C49, overview
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