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Literature summary for 2.2.1.9 extracted from

  • Fang, M.; Macova, A.; Hanson, K.L.; Kos, J.; Palmer, D.R.
    Using substrate analogues to probe the kinetic mechanism and active site of Escherichia coli MenD (2011), Biochemistry, 50, 8712-8721.
    View publication on PubMed
Search for more literature for 2.2.1.9

Protein Variants

Protein Variants Comment Organism
E55D about 30% decrease in catalytic efficiency Escherichia coli
I148L strong decrease in catalytic efficiency Escherichia coli
K292Q 150% increase in catalytic efficiency Escherichia coli
R107K no decrease in catalytic efficiency Escherichia coli
R293K slight increase in catalytic efficiency Escherichia coli
R395K 4fold increase in Km value, 50% decrease in kcat value Mycobacterium tuberculosis
R395K 90% decrease in catalytic efficiency Escherichia coli
R413K strong decrease in catalytic efficiency Escherichia coli
S32A slight decrease in catalytic efficiency Escherichia coli
S391A minor effect on activity Mycobacterium tuberculosis
S391A slight decrease in catalytic efficiency Escherichia coli
S391Y trace activity Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
4-[ethoxy(hydroxy)phosphoryl]-4-oxobutanoic acid inhibitor shows no significant inhibition of Mycobacterium tuberculosis growth in vitro under aerobic and hypoxic conditions Mycobacterium tuberculosis
4-[hydroxy(methoxy)phosphoryl]-4-oxobutanoic acid competitive with respect to 2-oxoglutarate, uncompetitive with respect to (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid. Compound is proposed to bind to the active site and react with thiamine diphosphate but not proceed forward to products by cleavage of the C-P bond Escherichia coli
4-[hydroxy(methoxy)phosphoryl]-4-oxobutanoic acid inhibitor shows no significant inhibition of Mycobacterium tuberculosis growth in vitro under aerobic and hypoxic conditions Mycobacterium tuberculosis
methyl succinylphosphonate dead-end inhibitor Escherichia coli

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0026
-
 2-oxoglutarate mutant K292Q, pH 7.4, temperature not specified in the publication Escherichia coli
0.0042
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R293K, pH 7.4, temperature not specified in the publication Escherichia coli
0.0053
-
 2-oxoglutarate mutant R107K, pH 7.4, temperature not specified in the publication Escherichia coli
0.0053
-
 isochorismate mutant R395K, pH 7.4, 25°C Mycobacterium tuberculosis
0.0091
-
 2-oxoglutarate mutant R293K, pH 7.4, temperature not specified in the publication Escherichia coli
0.0099
-
 2-oxoglutarate wild-type, pH 7.4, 25°C Mycobacterium tuberculosis
0.0099
-
 2-oxoglutarate wild-type, pH 7.4, temperature not specified in the publication Escherichia coli
0.0099
-
 2-oxoglutarate mutant S32A, pH 7.4, temperature not specified in the publication Escherichia coli
0.01
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R413K, pH 7.4, temperature not specified in the publication Escherichia coli
0.012
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid wild-type, pH 7.4, temperature not specified in the publication Escherichia coli
0.012
-
 2-oxoglutarate mutant E55D, pH 7.4, temperature not specified in the publication Escherichia coli
0.013
-
 2-oxoglutarate mutant S391A, pH 7.4, 25°C Mycobacterium tuberculosis
0.013
-
 2-oxoglutarate mutant S391A, pH 7.4, temperature not specified in the publication Escherichia coli
0.027
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant I418L, pH 7.4, temperature not specified in the publication Escherichia coli
0.036
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant S391A, pH 7.4, temperature not specified in the publication Escherichia coli
0.042
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant S32A, pH 7.4, temperature not specified in the publication Escherichia coli
0.045
-
 2-oxoglutarate mutant R395K, pH 7.4, 25°C Mycobacterium tuberculosis
0.045
-
 2-oxoglutarate mutant R395K, pH 7.4, temperature not specified in the publication Escherichia coli
0.05
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R292Q, pH 7.4, temperature not specified in the publication Escherichia coli
0.091
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R107K, pH 7.4, temperature not specified in the publication Escherichia coli
0.109
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R395K, pH 7.4, temperature not specified in the publication Escherichia coli
0.2
-
 2-oxoglutarate mutant I418L, pH 7.4, temperature not specified in the publication Escherichia coli
0.22
-
 2-oxoglutarate mutant R413K, pH 7.4, temperature not specified in the publication Escherichia coli

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ Km value 0.044 mM Escherichia coli
Mg2+ Km value of wild-type 0.044 mM, mutant S391A 0.013 mM Mycobacterium tuberculosis

Organism

Organism UniProt Comment Textmining
Escherichia coli
-
-
-
Mycobacterium tuberculosis
-
-
-

Reaction

Reaction Comment Organism Reaction ID
isochorismate + 2-oxoglutarate = 5-enolpyruvoyl-6-hydroxy-2-succinyl-cyclohex-3-ene-1-carboxylate + CO2 reaction follows a ping-pong bi-bi mechanism Escherichia coli
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid + 2-oxoglutarate analogue of isochorismate, weaker binding to enzyme. Only the (+)-enantiomer is a substrate Escherichia coli ? + CO2
-
 ?
isochorismate + 2-oxoglutarate
-
 Mycobacterium tuberculosis (1R,2S,5S,6S)-5-[(1-carboxyethenyl)oxy]-2-(3-carboxypropanoyl)-6-hydroxycyclohex-3-ene-1-carboxylic acid + CO2
-
 ?

Synonyms

Synonyms Comment Organism
MenD
-
 Escherichia coli
SEPHCHC synthase
-
 Escherichia coli

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.1
-
 2-oxoglutarate mutant R413K, pH 7.4, temperature not specified in the publication Escherichia coli
0.12
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R107K, pH 7.4, temperature not specified in the publication Escherichia coli
0.13
-
 2-oxoglutarate mutant R395K, pH 7.4, temperature not specified in the publication Escherichia coli
0.145
-
 2-oxoglutarate mutant R395K, pH 7.4, 25°C Mycobacterium tuberculosis
0.17
-
 2-oxoglutarate mutant R107K, pH 7.4, temperature not specified in the publication Escherichia coli
0.18
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R395K, pH 7.4, temperature not specified in the publication Escherichia coli
0.2
-
 2-oxoglutarate mutant K292Q, pH 7.4, temperature not specified in the publication Escherichia coli
0.22
-
 2-oxoglutarate mutant I418L, pH 7.4, temperature not specified in the publication Escherichia coli
0.22
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant S391A, pH 7.4, temperature not specified in the publication Escherichia coli
0.23
-
 2-oxoglutarate mutant S32A, pH 7.4, temperature not specified in the publication Escherichia coli
0.25
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant S32A, pH 7.4, temperature not specified in the publication Escherichia coli
0.28
-
 2-oxoglutarate wild-type, pH 7.4, 25°C Mycobacterium tuberculosis
0.28
-
 2-oxoglutarate wild-type, pH 7.4, temperature not specified in the publication Escherichia coli
0.28
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant K292Q, pH 7.4, temperature not specified in the publication Escherichia coli
0.3
-
 2-oxoglutarate mutant R293K, pH 7.4, temperature not specified in the publication Escherichia coli
0.3
-
 2-oxoglutarate mutant S391A, pH 7.4, 25°C Mycobacterium tuberculosis
0.3
-
 2-oxoglutarate mutant S391A, pH 7.4, temperature not specified in the publication Escherichia coli
0.38
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant I418L, pH 7.4, temperature not specified in the publication Escherichia coli
0.4
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid wild-type, pH 7.4, temperature not specified in the publication Escherichia coli
0.4
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R293K, pH 7.4, temperature not specified in the publication Escherichia coli

Cofactor

Cofactor Comment Organism Structure
thiamine diphosphate Km value 0.008 mM Escherichia coli
thiamine diphosphate Km value of wild-type 0.008 mM, mutant S391A 0.017 mM, mutant R395K 0.0022 mM, respectively Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00013
-
 4-[hydroxy(methoxy)phosphoryl]-4-oxobutanoic acid pH 7.4, temperature not specified in the publication Escherichia coli
0.0007
-
 4-[hydroxy(methoxy)phosphoryl]-4-oxobutanoic acid pH 7.4, 25°C Mycobacterium tuberculosis
0.016
-
 4-[ethoxy(hydroxy)phosphoryl]-4-oxobutanoic acid pH 7.4, 25°C Mycobacterium tuberculosis

General Information

General Information Comment Organism
physiological function enzyme is essential for menaquinone biosynthesis Escherichia coli

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.28
-
 2-oxoglutarate wild-type, pH 7.4, temperature not specified in the publication Escherichia coli
1
-
 2-oxoglutarate mutant I418L, pH 7.4, temperature not specified in the publication Escherichia coli
1
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R107K, pH 7.4, temperature not specified in the publication Escherichia coli
2
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R395K, pH 7.4, temperature not specified in the publication Escherichia coli
3
-
 2-oxoglutarate mutant R395K, pH 7.4, temperature not specified in the publication Escherichia coli
6
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant K292Q, pH 7.4, temperature not specified in the publication Escherichia coli
6
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant S32A, pH 7.4, temperature not specified in the publication Escherichia coli
6
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant S391A, pH 7.4, temperature not specified in the publication Escherichia coli
18
-
 2-oxoglutarate mutant E55D, pH 7.4, temperature not specified in the publication Escherichia coli
23
-
 2-oxoglutarate mutant S32A, pH 7.4, temperature not specified in the publication Escherichia coli
23
-
 2-oxoglutarate mutant S391A, pH 7.4, temperature not specified in the publication Escherichia coli
28
-
 2-oxoglutarate wild-type, pH 7.4, temperature not specified in the publication Escherichia coli
32
-
 2-oxoglutarate mutant R107K, pH 7.4, temperature not specified in the publication Escherichia coli
33
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid wild-type, pH 7.4, temperature not specified in the publication Escherichia coli
33
-
 2-oxoglutarate mutant R293K, pH 7.4, temperature not specified in the publication Escherichia coli
77
-
 2-oxoglutarate mutant K292Q, pH 7.4, temperature not specified in the publication Escherichia coli
95
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant R293K, pH 7.4, temperature not specified in the publication Escherichia coli
1417
-
 (+)-5-(carboxymethoxy)-6-hydroxycyclohexa-2,4-diene-1-carboxylic acid mutant I418L, pH 7.4, temperature not specified in the publication Escherichia coli