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Literature summary for 4.2.1.10 extracted from

  • Paz, S.; Tizon, L.; Otero, J.; Llamas-Saiz, A.; Fox, G.; Van Raaij, M.; Lamb, H.; Hawkins, A.; Lapthorn, A.; Castedo, L.; Gonzalez-Bello, C.
    Tetrahydrobenzothiophene derivatives: conformationally restricted inhibitors of type II dehydroquinase (2011), ChemMedChem, 6, 266-272.
    View publication on PubMed

Application

Application Comment Organism
drug development the enzyme is an attractive target for the development of new antimicrobials and herbicides Mycobacterium tuberculosis
drug development the enzyme is an attractive target for the development of new antimicrobials and herbicides Streptomyces coelicolor
drug development the enzyme is an attractive target for the development of new antimicrobials and herbicides Helicobacter pylori

Crystallization (Commentary)

Crystallization (Comment) Organism
DHQ2 in complex with inhibitors (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid and (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid, X-ray diffraction structure determination and analysis at 1.95 and 1.85 A resolution, respectively Helicobacter pylori

Inhibitors

Inhibitors Comment Organism Structure
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-nitrophenyl)cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Helicobacter pylori
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-nitrophenyl)cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Mycobacterium tuberculosis
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-phenoxyphenyl)cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Helicobacter pylori
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-phenoxyphenyl)cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Mycobacterium tuberculosis
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Helicobacter pylori
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Mycobacterium tuberculosis
(1R,4R,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Helicobacter pylori
(1R,4R,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Mycobacterium tuberculosis
(1R,4R,5R)-1,4,5-trihydroxy-3-[3-(phenylsulfanyl)phenyl]cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Helicobacter pylori
(1R,4R,5R)-1,4,5-trihydroxy-3-[3-(phenylsulfanyl)phenyl]cyclohex-2-ene-1-carboxylic acid a competitive inhibitor Mycobacterium tuberculosis
(1R,4S,5R)-3-(1-benzothiophen-2-ylmethoxy)-1,4,5-trihydroxycyclohex-2-ene-1-carboxylic acid a competitive inhibitor Helicobacter pylori
(1R,4S,5R)-3-(1-benzothiophen-2-ylmethoxy)-1,4,5-trihydroxycyclohex-2-ene-1-carboxylic acid a competitive inhibitor Mycobacterium tuberculosis
(3R,5R,6R)-3,5,6-trihydroxycyclohex-1-ene-1,3-dicarboxylic acid a competitive inhibitor Helicobacter pylori
(3R,5R,6R)-3,5,6-trihydroxycyclohex-1-ene-1,3-dicarboxylic acid a competitive inhibitor Mycobacterium tuberculosis
(4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
(4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Helicobacter pylori
(4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Mycobacterium tuberculosis
(4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
-
Streptomyces coelicolor
additional information inhibitor design and synthesis, binding structure and inhibition mechanism, overview Helicobacter pylori
additional information inhibitor design and synthesis, binding structure and inhibition mechanism, overview Mycobacterium tuberculosis
additional information inhibitor design and synthesis, binding structure and inhibition mechanism, overview Streptomyces coelicolor

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3-dehydroquinate Mycobacterium tuberculosis
-
3-dehydroshikimate + H2O
-
r
3-dehydroquinate Streptomyces coelicolor
-
3-dehydroshikimate + H2O
-
r
3-dehydroquinate Helicobacter pylori
-
3-dehydroshikimate + H2O
-
r

Organism

Organism UniProt Comment Textmining
Helicobacter pylori
-
-
-
Mycobacterium tuberculosis
-
-
-
Streptomyces coelicolor
-
-
-

Reaction

Reaction Comment Organism Reaction ID
3-dehydroquinate = 3-dehydroshikimate + H2O DHQ2 catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid through anti elimination of water, with the loss of the more acidic pro-S hydrogen from C-2 of 3-dehydroquinate. The elimination proceeds by a stepwise E1CB mechanism involving an enol intermediate. In the first step, an essential tyrosine in the active site removes the pro-S hydrogen from C-2 of 1. The final step is the acid-catalyzed elimination of the C-1 hydroxy group, a reaction catalyzed by a histidine, which acts as a proton donor, reaction mechanism, overview Mycobacterium tuberculosis
3-dehydroquinate = 3-dehydroshikimate + H2O DHQ2 catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid through anti elimination of water, with the loss of the more acidic pro-S hydrogen from C-2 of 3-dehydroquinate. The elimination proceeds by a stepwise E1CB mechanism involving an enol intermediate. In the first step, an essential tyrosine in the active site removes the pro-S hydrogen from C-2 of 1. The final step is the acid-catalyzed elimination of the C-1 hydroxy group, a reaction catalyzed by a histidine, which acts as a proton donor, reaction mechanism, overview Streptomyces coelicolor
3-dehydroquinate = 3-dehydroshikimate + H2O DHQ2 catalyzes the reversible dehydration of 3-dehydroquinic acid to form 3-dehydroshikimic acid through anti elimination of water, with the loss of the more acidic pro-S hydrogen from C-2 of 3-dehydroquinate. The elimination proceeds by a stepwise E1CB mechanism involving an enol intermediate. In the first step, an essential tyrosine in the active site removes the pro-S hydrogen from C-2 of 1. The final step is the acid-catalyzed elimination of the C-1 hydroxy group, a reaction catalyzed by a histidine, which acts as a proton donor, reaction mechanism, overview Helicobacter pylori

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3-dehydroquinate
-
Mycobacterium tuberculosis 3-dehydroshikimate + H2O
-
r
3-dehydroquinate
-
Streptomyces coelicolor 3-dehydroshikimate + H2O
-
r
3-dehydroquinate
-
Helicobacter pylori 3-dehydroshikimate + H2O
-
r

Synonyms

Synonyms Comment Organism
DHQ2
-
Mycobacterium tuberculosis
DHQ2
-
Streptomyces coelicolor
DHQ2
-
Helicobacter pylori
Type II dehydroquinase
-
Mycobacterium tuberculosis
Type II dehydroquinase
-
Streptomyces coelicolor
Type II dehydroquinase
-
Helicobacter pylori

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Mycobacterium tuberculosis
25
-
assay at Streptomyces coelicolor
25
-
assay at Helicobacter pylori

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Mycobacterium tuberculosis
7.5
-
assay at Streptomyces coelicolor
7.5
-
assay at Helicobacter pylori

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000054
-
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-nitrophenyl)cyclohex-2-ene-1-carboxylic acid pH not specified in the publication, temperature not specified in the publication Mycobacterium tuberculosis
0.00012
-
(1R,4R,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid pH not specified in the publication, temperature not specified in the publication Mycobacterium tuberculosis
0.00013
-
(1R,4S,5R)-3-(1-benzothiophen-2-ylmethoxy)-1,4,5-trihydroxycyclohex-2-ene-1-carboxylic acid pH not specified in the publication, temperature not specified in the publication Helicobacter pylori
0.00025
-
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid pH not specified in the publication, temperature not specified in the publication Mycobacterium tuberculosis
0.00038
-
(1R,4R,5R)-1,4,5-trihydroxy-3-[3-(phenylsulfanyl)phenyl]cyclohex-2-ene-1-carboxylic acid pH not specified in the publication, temperature not specified in the publication Mycobacterium tuberculosis
0.00049
-
(1R,4R,5R)-1,4,5-trihydroxy-3-(3-phenoxyphenyl)cyclohex-2-ene-1-carboxylic acid pH not specified in the publication, temperature not specified in the publication Helicobacter pylori
0.00054
-
(1R,4R,5R)-1,4,5-trihydroxy-3-(thiophen-2-yl)cyclohex-2-ene-1-carboxylic acid pH not specified in the publication, temperature not specified in the publication Helicobacter pylori
0.00094
-
(3R,5R,6R)-3,5,6-trihydroxycyclohex-1-ene-1,3-dicarboxylic acid pH not specified in the publication, temperature not specified in the publication Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00000084
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0000011
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.000022
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.000049
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.000052
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.000069
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00009
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.000093
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.000097
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00011
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.000122
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-4,6,7-trihydroxy-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00019
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0003
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00032
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00032
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-2-ethyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00035
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-4,6,7-trihydroxy-2-[(1Z)-prop-1-en-1-yl]-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0004
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0006
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-2-(1-cyclopropylethyl)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00081
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00086
-
pH 7.5, 25°C Mycobacterium tuberculosis (4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00108
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-2-[(1E)-2-cyclopropylprop-1-en-1-yl]-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00126
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-2-ethenyl-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0016
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0018
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0019
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.00315
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-4,6,7-trihydroxy-2-methyl-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0034
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-4,6,7-trihydroxy-2-(propan-2-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.0097
-
pH 7.5, 25°C Streptomyces coelicolor (4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.034
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-4,6,7-trihydroxy-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid
0.038
-
pH 7.5, 25°C Helicobacter pylori (4R,6R,7S)-4,6,7-trihydroxy-2-(prop-2-en-1-yl)-4,5,6,7-tetrahydro-1-benzothiophene-4-carboxylic acid