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Literature summary for 4.2.1.10 extracted from

  • Dias, M.V.; Snee, W.C.; Bromfield, K.M.; Payne, R.J.; Palaninathan, S.K.; Ciulli, A.; Howard, N.I.; Abell, C.; Sacchettini, J.C.; Blundell, T.L.
    Structural investigation of inhibitor designs targeting 3-dehydroquinate dehydratase from the shikimate pathway of Mycobacterium tuberculosis (2011), Biochem. J., 436, 729-739.
    View publication on PubMed
Search for more literature for 4.2.1.10

Application

Application Comment Organism
drug development absence of the shikimate patway from humans makes the enzymes of this pathway potential drug targets Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
gene aroD, expression in Escherichia coli strain BL21(DE3) as His6-tagged protein. The enzyme is cloned with a thrombin cleavage site or the pET28b vector with a modified tobacco etch virus cleavage site after the N-terminal His6 tag Mycobacterium tuberculosis

Crystallization (Commentary)

Crystallization (Comment) Organism
enzyme in complex with product 3-dehydroshikimate, X-ray diffraction structure determination and analysis Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
(1R,4R,5R)-1,4,5-trihydroxy-3-[3-phenoxy-prop-(E)-enyl]-cyclohex-2-enecarboxylic acid
-
 Mycobacterium tuberculosis
(1R,4R,5R)-3-(tert-butylcarbamoyl)-1,4,5-trihydroxycyclohex-2-enecarboxylic acid
-
 Mycobacterium tuberculosis
(1R,4S,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid
-
 Mycobacterium tuberculosis
(1S,4R,5R)-3-(3-benzoylphenyl)-1,4,5-trihydroxycyclohex-2-enecarboxylic acid
-
 Mycobacterium tuberculosis
2,3-anhydroquinate mimics the flattened enol/enolate reaction intermediate and serves as an anchor molecule for four of the inhibitors investigated, overview. Structure of MtDHQase in complex with a 2,3-anhydroquinate moiety attached to a biaryl group shows that this group extends to an active-site subpocket inducing significant structural rearrangement Mycobacterium tuberculosis
citrazinic acid a planar analogue of the reaction product, complex structure, overview Mycobacterium tuberculosis
additional information active-site binding of inhibitors, structure, overview Mycobacterium tuberculosis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WPX7 gene Rv2537c or aroD
-
Mycobacterium tuberculosis H37Rv P9WPX7 gene Rv2537c or aroD
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His6-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, cleavage of the His-tag, and gel filtration Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information active-site binding of 3-dehydroshikimate, catalytic loop in the MtDHQase-1 structure, comparison with the incomplete structure of apo-MtDHQase, PDB code 2DHQ, overview Mycobacterium tuberculosis ?
-
 ?
additional information active-site binding of 3-dehydroshikimate, catalytic loop in the MtDHQase-1 structure, comparison with the incomplete structure of apo-MtDHQase, PDB code 2DHQ, overview Mycobacterium tuberculosis H37Rv ?
-
 ?

Synonyms

Synonyms Comment Organism
dehydroquinase
-
 Mycobacterium tuberculosis
MtDHQase
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
 assay at Mycobacterium tuberculosis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00014
-
 (1R,4R,5R)-1,4,5-trihydroxy-3-[3-phenoxy-prop-(E)-enyl]-cyclohex-2-enecarboxylic acid recombinant enzyme, pH 7.0, 25°C Mycobacterium tuberculosis
0.0023
-
 (1R,4S,5R)-1,4,5-trihydroxy-3-[(1E)-3-phenoxyprop-1-en-1-yl]cyclohex-2-ene-1-carboxylic acid recombinant enzyme, pH 7.0, 25°C Mycobacterium tuberculosis
0.011
-
 (1S,4R,5R)-3-(3-benzoylphenyl)-1,4,5-trihydroxycyclohex-2-enecarboxylic acid recombinant enzyme, pH 7.0, 25°C Mycobacterium tuberculosis
0.027
-
 (1R,4R,5R)-3-(tert-butylcarbamoyl)-1,4,5-trihydroxycyclohex-2-enecarboxylic acid recombinant enzyme, pH 7.0, 25°C Mycobacterium tuberculosis
0.2
-
 2,3-anhydroquinate recombinant enzyme, pH 7.0, 25°C Mycobacterium tuberculosis
0.3
-
 citrazinic acid recombinant enzyme, pH 7.0, 25°C Mycobacterium tuberculosis

General Information

General Information Comment Organism
metabolism the enzyme is the third enzyme of the shikimate pathway, which is essential in Mycobacterium tuberculosis Mycobacterium tuberculosis