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Literature summary extracted from

  • 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 (2016), Biochem. Biophys. Res. Commun., 478, 1688-1693.
    View publication on PubMed

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.1.1.286 recombinant expression in Escherichia coli strain Escherichia coli BL21(DE3)CodonPlus-RIL Thermus thermophilus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.1.1.286 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 Thermus thermophilus

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.1.1.286 (2S,3S)-thiahomoisocitrate
-
 Thermus thermophilus

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.1.1.286 0.21
-
 homoisocitrate pH 8.0, 60°C, recombinant enzyme Thermus thermophilus
1.1.1.286 0.29
-
 isocitrate pH 8.0, 60°C, recombinant enzyme Thermus thermophilus

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
1.1.1.286 Mg2+ binding strutcure analysis Thermus thermophilus

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.1.1.286 homoisocitrate + NAD+ Thermus thermophilus
-
 2-oxoadipate + CO2 + NADH + H+
-
 r
1.1.1.286 homoisocitrate + NAD+ Thermus thermophilus DSM 7039
-
 2-oxoadipate + CO2 + NADH + H+
-
 r
1.1.1.286 isocitrate + NAD+ Thermus thermophilus
-
 2-oxoglutarate + CO2 + NADH + H+
-
 r
1.1.1.286 isocitrate + NAD+ Thermus thermophilus DSM 7039
-
 2-oxoglutarate + CO2 + NADH + H+
-
 r
1.1.1.286 additional information Thermus thermophilus 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 ?
-
 ?
1.1.1.286 additional information Thermus thermophilus DSM 7039 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 ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.1.1.286 Thermus thermophilus Q72IW9
-
-
1.1.1.286 Thermus thermophilus DSM 7039 Q72IW9
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.1.1.286 recombinant enzyme from Escherichia coli by anion exchange chromatography, ammonium sufate fractionation, hydrophobic interaction chromatography, and gel filtration Thermus thermophilus

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.1.1.286 homoisocitrate + NAD+
-
 Thermus thermophilus 2-oxoadipate + CO2 + NADH + H+
-
 r
1.1.1.286 homoisocitrate + NAD+
-
 Thermus thermophilus DSM 7039 2-oxoadipate + CO2 + NADH + H+
-
 r
1.1.1.286 isocitrate + NAD+
-
 Thermus thermophilus 2-oxoglutarate + CO2 + NADH + H+
-
 r
1.1.1.286 isocitrate + NAD+
-
 Thermus thermophilus DSM 7039 2-oxoglutarate + CO2 + NADH + H+
-
 r
1.1.1.286 additional information 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 Thermus thermophilus ?
-
 ?
1.1.1.286 additional information dual substrate specificity for homoisocitrate dehydrogenase Thermus thermophilus ?
-
 ?
1.1.1.286 additional information 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 Thermus thermophilus DSM 7039 ?
-
 ?
1.1.1.286 additional information dual substrate specificity for homoisocitrate dehydrogenase Thermus thermophilus DSM 7039 ?
-
 ?

Subunits

EC Number Subunits Comment Organism
1.1.1.286 tetramer dimer of dimers Thermus thermophilus

Synonyms

EC Number Synonyms Comment Organism
1.1.1.286 HICDH
-
 Thermus thermophilus

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.1.1.286 60
-
 assay at Thermus thermophilus

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.1.1.286 33
-
 homoisocitrate pH 8.0, 60°C, recombinant enzyme Thermus thermophilus
1.1.1.286 76
-
 isocitrate pH 8.0, 60°C, recombinant enzyme Thermus thermophilus

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.1.1.286 8
-
 assay at Thermus thermophilus

Cofactor

EC Number Cofactor Comment Organism Structure
1.1.1.286 NAD+
-
 Thermus thermophilus
1.1.1.286 NADH 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+ Thermus thermophilus

General Information

EC Number General Information Comment Organism
1.1.1.286 evolution homoisocitrate dehydrogenase, HICDH, is a member of the beta-decarboxylating dehydrogenase family Thermus thermophilus
1.1.1.286 metabolism 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 Thermus thermophilus
1.1.1.286 additional information 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 Thermus thermophilus

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1.1.1.286 157.1
-
 homoisocitrate pH 8.0, 60°C, recombinant enzyme Thermus thermophilus
1.1.1.286 262.1
-
 isocitrate pH 8.0, 60°C, recombinant enzyme Thermus thermophilus