Requires Mn2+ and K+ or NH4+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+) and EC 1.1.1.87, homoisocitrate dehydrogenase, this enzyme, from Pyrococcus horikoshii, can use both isocitrate and homoisocitrate as substrates. The enzyme may play a role in both the lysine and glutamate biosynthesis pathways.
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The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota
chemical mechanism on the basis of the pH dependence of kinetic parameters, dissociation constants for competitive inhibitors, and multiple-substrate deuterium/13C isotope effects suggesting a stepwise mechanism with hydride transfer preceding decarboxylation, the decarboxylation step contributes only slightly to rate limitation, overview
chemical mechanism on the basis of the pH dependence of kinetic parameters, dissociation constants for competitive inhibitors, and multiple-substrate deuterium/13C isotope effects suggesting a stepwise mechanism with hydride transfer preceding decarboxylation, the decarboxylation step contributes only slightly to rate limitation, overview
Requires Mn2+ and K+ or NH4+ for activity. Unlike EC 1.1.1.41, isocitrate dehydrogenase (NAD+) and EC 1.1.1.87, homoisocitrate dehydrogenase, this enzyme, from Pyrococcus horikoshii, can use both isocitrate and homoisocitrate as substrates. The enzyme may play a role in both the lysine and glutamate biosynthesis pathways.
the enzyme catalyzes the fourth reaction of the alpha-aminoadipate pathway for lysine biosynthesis, the conversion of homoisocitrate to alpha-ketoadipate using NAD+ as an oxidizing agent
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
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
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
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
the enzyme catalyzes the fourth reaction of the alpha-aminoadipate pathway for lysine biosynthesis, the conversion of homoisocitrate to alpha-ketoadipate using NAD+ as an oxidizing agent
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
Saci_2375 exhibits distinct and similar activities for isocitrate and homoisocitrate, but no detectable activity for 3-isopropylmalate. Saci_2375 is a dual function enzyme serving as isocitrate-homoisocitrate dehydrogenase
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
in contrast to other homoisicitrate dehydrogenases, the homoisocitrate dehydrogenase from the thermophilic bacterium Thermus thermophilus (TtHICDH) catalyzes the reactions using both homoisocitrate and isocitrate as substrates at similar efficiencies
NADH forms specific contacts with enzyme TtHICDH. The 2'- and 3-OHs of the adenine ribose of NADH form hydrogen bonds with Asp265 conserved among HICDHs, which may serve as a determinant for the preference of HICDH family members for NAD+ to NADP+
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
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
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
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
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
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
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
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
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
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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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant His6-tagged enzyme in apoform or in complex with substrates isocitrate, homoisocitrate, and 3-isopropylmalate, hanging drop vapour diffusion method, for the apoenzyme: mixing of 0.001 ml of 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, and 150 mM NaCl, with 0.001 ml of reservoir solution containing 100 mM imidazole-HCl, pH 6.5, and 2.3 M NaCl, equilibration against 1 m of reservoir solution, at 20°C, for the ternary complex with homoisocitrate and Mn2+: mixing of 0.0015 ml of 10 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 150 mM NaCl, 10% glycerol, 1 mM MnSO4, and 5 mM homoisocitrate, with 0.0015 ml of reservoir solution containing 100 mM HEPES-NaOH, pH 7.5, 200 mM NaCl, and 10% v/v 2-propanol, at 20°C, for the ternary complex with homoisocitrate and Mn2+: mixing of 0.0015 ml of 5 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 150 mM NaCl, 10% glycerol, 1 mM MnSO4, and 5 mM isocitrate, with 0.0015 ml of reservoir solution containing 100 mM TrisHCl, pH 7.5, 200 mM NaCl, and 30% v/v 2-methyl-2,4-pentanediol, at 20°C, and for the ternary complex with 3-isopropylmalate and Mn2+: mixing of 0.001 ml of 15 mg/ml protein in 20 mM Tris-HCl, pH 8.0, 150 mM NaCl, 10% glycerol, 1 mM MnSO4, and 5 mM 3-isopropylmalate, with 0.001 ml of reservoir solution containing 100 mM HEPES-NaOH, pH 7.5, 200 mM NaCl, and 36% v/v 2-methyl-2,4-pentanediol, at 20°C, X-ray diffraction structure determination and analysis at 1.7 A resolution for the apoenzyme, and at 2.50-2.64 A resolution for the complexed enzyme
purified enzyme TtHICDH in quaternary complex with homoisocitrate, NADH, and Mg2+, X-ray diffraction strczure determination and analysis at 2.5 A resolution, molecular replacement using the apoform of TtHICDH, PDB ID 1X0L, at a resolution of 2.5 A
generation of a gene-disruption TK0280 deletion mutan strain, functional complementation by expression of the gene icdh from Thermus thermophilus strain Hb27, but not by genes hicdh and leuB from this organism
generation of a gene-disruption TK0280 deletion mutan strain, functional complementation by expression of the gene icdh from Thermus thermophilus strain Hb27, but not by genes hicdh and leuB from this organism
recombinant enzyme from Escherichia coli by anion exchange chromatography, ammonium sufate fractionation, hydrophobic interaction chromatography, and gel filtration
recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21-CodonPlus (DE3)-RIL by nickel affinity chromatography and gel filtration
Miyazaki, J.; Kobashi, N.; Nishiyama, M.; Yamane, H.
Characterization of homoisocitrate dehydrogenase involved in lysine biosynthesis of an extremely thermophilic bacterium, Thermus thermophilus HB27, and evolutionary implication of beta-decarboxylating dehydrogenase
Identification of a novel trifunctional homoisocitrate dehydrogenase and modulation of the broad substrate specificity through site-directed mutagenesis
Takahashi, K.; Tomita, T.; Kuzuyama, T.; Nishiyama, M.
Determinants of dual substrate specificity revealed by the crystal structure of homoisocitrate dehydrogenase from Thermus thermophilus in complex with homoisocitrate-Mg(2+)-NADH