Information on EC 1.1.1.286 - isocitrate-homoisocitrate dehydrogenase

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HICDH

6 entries

homoisocitrate dehydrogenase

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685232, 696220

isocitrate-homoisocitrate dehydrogenase

Saci_2375

TK0280

additional information

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HIcDH is a member of the family of pyridine nucleotide-linked beta-hydroxy acid oxidative decarboxylases

(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+ = 2-oxoadipate + CO2 + NADH + H+

isocitrate + NAD+ = 2-oxoglutarate + CO2 + NADH

citric acid cycle, lysine metabolism

BRENDA

KEGG

Biosynthesis of secondary metabolites, Citrate cycle (TCA cycle), Lysine biosynthesis, Microbial metabolism in diverse environments

MetaCyc

coenzyme B biosynthesis, L-lysine biosynthesis IV, L-lysine biosynthesis V, nitrogen remobilization from senescing leaves, TCA cycle II (plants and fungi), TCA cycle III (animals)

isocitrate(homoisocitrate):NAD+ oxidoreductase (decarboxylating)

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.

9001-58-5

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9067-90-7

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(1R,2S)-1-hydroxybutane-1,2,4-tricarboxylate + NAD+

2-oxoadipate + CO2 + NADH + H+

-

Substrates: chemical mechanism, stereochemistry of hydride transfer to NAD, overview
Products: -

?

3-isopropylmalate + NAD+

2-oxoisocaproate + CO2 + NADH + H+

3-isopropylmalate + NAD+

?

-

Substrates: at 0.1% of the rate with homoisocitrate
Products: -

?

homoisocitrate + NAD+

2-oxoadipate + CO2 + NADH + H+

homoisocitrate + NAD+

? + NADH

5 entries

homoisocitrate + NADP+

2-oxoadipate + CO2 + NADPH + H+

isocitrate + NAD+

2-oxoglutarate + CO2 + NADH + H+

10 entries

isocitrate + NADP+

2-oxoglutarate + CO2 + NADPH + H+

additional information

?

-

14 entries

homoisocitrate + NAD+

2-oxoadipate + CO2 + NADH + H+

homoisocitrate + NAD+

? + NADH

-

Substrates: -
Products: -

?

homoisocitrate + NADP+

2-oxoadipate + CO2 + NADPH + H+

isocitrate + NAD+

2-oxoglutarate + CO2 + NADH + H+

isocitrate + NADP+

2-oxoglutarate + CO2 + NADPH + H+

additional information

?

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NAD+

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+

Sulfolobus acidocaldarius

NADP+

Sulfolobus acidocaldarius

Saci_2375 is an NADP+-dependent enzyme with the ability to function as ICDH, EC 1.1.1.42, and HICDH, EC 1.1.1.87

738195

NADPH

Saci_2375 is an NADP+-dependent enzyme with the ability to function as ICDH, EC 1.1.1.42, and HICDH, EC 1.1.1.87

K+

Mg2+

Mn2+

NH4+

-

200 mM activates by 80.9%

Rb+

-

200 mM activates by 29.3%

additional information

-

200 mM Cs+, Li+, and Na+ do not activate

(2S,3S)-thiahomoisocitrate

Thermus thermophilus

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3-carboxypropylidenemalate

Cl-

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homoisocitrate

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competitive, pH-dependent substrate inhibition

isocitrate

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competitive, pH-dependent substrate inhibition

K+

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absolute requirement, inhibitory above 0.4 M

Mn2+

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inhibitory above 1 mM

NADH

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product inhibitor

NH4+

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may substitute for K+, inhibitory above 0.2 M

potassium acetate

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0.05 - 1.33

3-isopropylmalate

5 entries

0.0073 - 7.486

homoisocitrate

14 entries

0.014 - 2.2

isocitrate

12 entries

0.036 - 1.8

NAD+

18 entries

additional information

-

0.371 - 9.4

3-isopropylmalate

5 entries

4.8 - 171

homoisocitrate

14 entries

0.22 - 171

isocitrate

12 entries

21.8 - 30.3

NAD+

2.2 - 46

3-isopropylmalate

5.3 - 3364

homoisocitrate

8 entries

0.44 - 2259

isocitrate

8 entries

0.56 - 470

NAD+

16 entries

0.043

3-carboxypropylidenemalate

-

pH 8.0, 25°C, versus homoisocitrate

90

Cl-

-

2.7

NADH

-

500

potassium acetate

-

8

5 - 10

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pH-profile, overview

25

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assay at

60

3 entries

-

-

Pyrococcus horikoshii

expression in Escherichia coli

660907

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Sulfolobus acidocaldarius

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685232, 696220

-

-

738195

Sulfolobus acidocaldarius MW001

UniProt

-

738195

Thermococcus kodakarensis

UniProt

-

740021

Q5JFV8

UniProt

Thermococcus kodakarensis KRD1

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UniProt

Thermus thermophilus DSM 7039

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Swissprot

Thermus thermophilus HB27 / ATCC BAA-163 / DSM 7039

expression in Escherichia coli

656127

Swissprot

Highest Expressing Human Cell Lines

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Cell Line Links

Gene Links

evolution

metabolism

physiological function

additional information

154000

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gel filtration

35727

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4 * 35751, mass spectrometry, 4 * 35727, calculated

35751

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4 * 35751, mass spectrometry, 4 * 35727, calculated

tetramer

7 entries

additional information

Thermococcus kodakarensis

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

Q5JFV8

740021

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

R85V

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increased ability to use 3-isopropylmalate

R87T

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uses substrate homoisocitrate, but not substrates isocitrate or 3-isopropylmalate

R87V

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uses substrate homoisocitrate, but not substrates isocitrate or 3-isopropylmalate