1.1.1.286: isocitrate-homoisocitrate dehydrogenase
This is an abbreviated version!
For detailed information about isocitrate-homoisocitrate dehydrogenase, go to the full flat file.
Reaction
Synonyms
3-carboxy-2-hydroxyadipate dehydrogenase, HICDH, homoisocitrate dehydrogenase, isocitrate-homoisocitrate dehydrogenase, More, Saci_2375, TK0280
ECTree
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General Information
General Information on EC 1.1.1.286 - isocitrate-homoisocitrate dehydrogenase
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evolution
metabolism
physiological function
additional information
homoisocitrate dehydrogenase, HICDH, is a member of the beta-decarboxylating dehydrogenase family
evolution
TK0280 from Thermococcus kodakarensis is an ancestral-type beta-decarboxylating dehydrogenase. beta-Decarboxylating dehydrogenases, which are involved in central metabolism, are considered to have diverged from a common ancestor with broad substrate specificity, phylogenetic analysis, overview
evolution
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TK0280 from Thermococcus kodakarensis is an ancestral-type beta-decarboxylating dehydrogenase. beta-Decarboxylating dehydrogenases, which are involved in central metabolism, are considered to have diverged from a common ancestor with broad substrate specificity, phylogenetic analysis, overview
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evolution
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homoisocitrate dehydrogenase, HICDH, is a member of the beta-decarboxylating dehydrogenase family
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in contrast to other homoisocitrate dehydrogenases, the enzyme from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies. The enzyme catalyzes the conversion of homoisocitrate to 2-oxoadipate using NAD+ as a coenzyme, which is the fourth reaction involved in lysine biosynthesis through the alpha-aminoadipate pathway
metabolism
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in contrast to other homoisocitrate dehydrogenases, the enzyme from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies. The enzyme catalyzes the conversion of homoisocitrate to 2-oxoadipate using NAD+ as a coenzyme, which is the fourth reaction involved in lysine biosynthesis through the alpha-aminoadipate pathway
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recombinant enzyme TK0280 exhibits dehydrogenase activities toward homoisocitrate, isocitrate, and 3-isopropylmalate, which correspond to key reactions involved in the lysine biosynthetic pathway, tricarboxylic acid cycle, and leucine biosynthetic pathway, respectively. TK0280 functions as both an isocitrate dehydrogenase and homoisocitrate dehydrogenase in Thermococcus kodakarensis, but not as a 3-isopropylmalate dehydrogenase, most probably reflecting its low catalytic efficiency toward 3-isopropylmalate
physiological function
the failure to isolate a knockout mutant of saci_2375 suggests the indispensable role of Saci_2375 in cell viability
physiological function
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the failure to isolate a knockout mutant of saci_2375 suggests the indispensable role of Saci_2375 in cell viability
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physiological function
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recombinant enzyme TK0280 exhibits dehydrogenase activities toward homoisocitrate, isocitrate, and 3-isopropylmalate, which correspond to key reactions involved in the lysine biosynthetic pathway, tricarboxylic acid cycle, and leucine biosynthetic pathway, respectively. TK0280 functions as both an isocitrate dehydrogenase and homoisocitrate dehydrogenase in Thermococcus kodakarensis, but not as a 3-isopropylmalate dehydrogenase, most probably reflecting its low catalytic efficiency toward 3-isopropylmalate
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enzyme structure modelling and molecular dynamics, the distal carboxyl group of homoiscitrate is recognized by the side chains of Ser72 and Arg85 from one subunit, and Asn173 from another subunit of a dimer unit. The enzyme recognizes the distal carboxyl group of isocitrate by Arg85 in the model. Active site structure analysis, the active site is located in the cleft between two domains. In the quaternary complex of TtHICDH, the basic residues, Arg88, Arg96, Arg118, Tyr125, and Lys171, recognize the malate moiety of HIC. Asp204 (from the otherdimer part) , Asp228, Asp232, and water molecules bind a Mg2+ ion in an octahedral coordination manner similar to those of other substrate-bound structures, e.g. PDB ID 4F7I
additional information
residues Thr71 and Ser80 play important roles in the recognition of homoisocitrate and isocitrate while the hydrophobic region consisting of Ile82 and Leu83 is responsible for the recognition of 3-isopropylmalate. Importance of a water-mediated hydrogen bond network for the stabilization of the beta3-alpha4 loop, including the Thr71 residue, with respect to the promiscuity of the substrate specificity of TK0280. Structural basis of substrate promiscuity, conformational changes upon binding of substrates and active site structure, overview
additional information
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residues Thr71 and Ser80 play important roles in the recognition of homoisocitrate and isocitrate while the hydrophobic region consisting of Ile82 and Leu83 is responsible for the recognition of 3-isopropylmalate. Importance of a water-mediated hydrogen bond network for the stabilization of the beta3-alpha4 loop, including the Thr71 residue, with respect to the promiscuity of the substrate specificity of TK0280. Structural basis of substrate promiscuity, conformational changes upon binding of substrates and active site structure, overview
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additional information
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enzyme structure modelling and molecular dynamics, the distal carboxyl group of homoiscitrate is recognized by the side chains of Ser72 and Arg85 from one subunit, and Asn173 from another subunit of a dimer unit. The enzyme recognizes the distal carboxyl group of isocitrate by Arg85 in the model. Active site structure analysis, the active site is located in the cleft between two domains. In the quaternary complex of TtHICDH, the basic residues, Arg88, Arg96, Arg118, Tyr125, and Lys171, recognize the malate moiety of HIC. Asp204 (from the otherdimer part) , Asp228, Asp232, and water molecules bind a Mg2+ ion in an octahedral coordination manner similar to those of other substrate-bound structures, e.g. PDB ID 4F7I
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