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Literature summary for 5.4.99.5 extracted from

  • Khanapur, M.; Alvala, M.; Prabhakar, M.; Shiva Kumar, K.; Edwin, R.K.; Sri Saranya, P.S.; Patel, R.K.; Bulusu, G.; Misra, P.; Pal, M.
    Mycobacterium tuberculosis chorismate mutase a potential target for TB (2017), Bioorg. Med. Chem., 25, 1725-1736 .
    View publication on PubMed
Search for more literature for 5.4.99.5

Application

Application Comment Organism
drug development the secretory isozyme is a target for the discovery of anti-tubercular agents Mycobacterium tuberculosis

Cloned(Commentary)

Cloned (Comment) Organism
the Rv1885c gene product is synthesized with an N-terminal signal sequence of 33 amino acids, which is cleaved off upon heterologous expression in Escherichia coli, and transported into the periplasmic space Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
(1R,3R,5S,8R)-8-hydroxy-2-oxabicyclo[3.3.1]non-6-ene-3,5-dicarboxylic acid
-
 Mycobacterium tuberculosis
(1R,3R,5S,8R)-8-hydroxy-5-nitro-2-azabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
 Mycobacterium tuberculosis
(1R,3R,5S,8R)-8-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
 Mycobacterium tuberculosis
(1R,3S,5S,8R)-8-hydroxy-2-oxabicyclo[3.3.1]non-6-ene-3,5-dicarboxylic acid
-
 Mycobacterium tuberculosis
(1R,3S,5S,8R)-8-hydroxy-5-nitro-2-oxabicyclo[3.3.1]non-6-ene-3-carboxylic acid
-
 Mycobacterium tuberculosis
(1R,3S,6S,8S,10S)-10-hydroxy-4-oxo-5-oxa-2-azatricyclo[4.3.1.13,8]undecane-8-carboxylic acid
-
 Mycobacterium tuberculosis
(1R,5R,8R)-8-hydroxy-2-oxabicyclo[3.3.1]nona-3,6-diene-3,5-dicarboxylic acid
-
 Mycobacterium tuberculosis
(1R,5S,8R)-8-hydroxy-2-azabicyclo[3.3.1]non-6-ene-3,5-dicarboxylic acid
-
 Mycobacterium tuberculosis
(1S,2aR,2bR,3S)-4-oxohexahydro-1H-5-oxa-2b-aza-1,3-methanocyclopropa[cd]indene-1-carboxylic acid
-
 Mycobacterium tuberculosis
(2Z)-2-(4-chlorophenyl)-3-[4-(dimethoxymethyl)-2-nitrophenyl]prop-2-enoic acid competitive Mycobacterium tuberculosis
(Z)-3-(4-nitrobenzylidene)indolin-2-one MIC is 0.0235 mM Mycobacterium tuberculosis
1-(2-(tert-butyl)-5-chloro-7-(methylsulfonyl)-1H-indol-3-yl)ethan-1-one 45% inhibition at 0.03 mM Mycobacterium tuberculosis
1-aminoadamantane
-
 Mycobacterium tuberculosis
1-hydroxyadamantane
-
 Mycobacterium tuberculosis
2-chloro-3-(5,6-difluoro-1H-indol-3-yl)quinoxaline
-
 Mycobacterium tuberculosis
2-chloro-4-(ethoxycarbonyl)-1-hydroxy-6-methylquinolin-1-ium
-
 Mycobacterium tuberculosis
2-[2-[3-(tert-butoxycarbonyl)-2-phenyl-1,3-thiazolidin-4-yl]ethyl]-4-methylpentanoic acid competitive Mycobacterium tuberculosis
3-((dihydroxyamino)thio)-4-((3,5-dimethoxyphenethyl)amino)-5-nitrobenzoic acid competitive Mycobacterium tuberculosis
3-(3-methoxyphenyl)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3d]pyrimidin-4[3H]-one
-
 Mycobacterium tuberculosis
3-amino-1-(3-(4-hydroxybut-1-yn-1-yl)phenyl)-1H-benzol[f]chromene-2-carbonitril
-
 Mycobacterium tuberculosis
3-chloroadamantane
-
 Mycobacterium tuberculosis
5-naphthyl-7-propyl-3H-pyrazolo-[4,3-d][1,2,3]triazin-4[5h]-one
-
 Mycobacterium tuberculosis
6'-iodo-1,3-dihydro-1'H-spiro[indene-2,2'-quinazolin]-4'(3'H)-one a spiro 2,3-dihydroquinazolin-4(1H)-one Mycobacterium tuberculosis
6,6'-dinitro-[1,1'-biphenyl]-2,2'-dicarboxylic acid
-
 Mycobacterium tuberculosis
6-hydroxyadamantane
-
 Mycobacterium tuberculosis
6-hydroxybicyclo[3.3.1]nonane-1,3-dicarboxylic acid
-
 Mycobacterium tuberculosis
adamantan phosphonic acid
-
 Mycobacterium tuberculosis
Adamantane-1-acetic acid
-
 Mycobacterium tuberculosis
adamantane-1-carboxylic acid
-
 Mycobacterium tuberculosis
carvacrol
-
 Mycobacterium tuberculosis
ethyl 4-(2-(4-hydroxybut-1-yn-1-yl)phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
-
 Mycobacterium tuberculosis
indoline-2,3-dione
-
 Mycobacterium tuberculosis
methyl 4-(methylamino)-3-nitrobenzoate competitive Mycobacterium tuberculosis
additional information development and synthesis of transition state analogues and small molecule compounds as enzyme inhibitors Mycobacterium tuberculosis
N-(4-fluoro-2-(5-fluoro-1-(methylsulfonyl)-1H-inden-2-yl)phenyl)methanesulfonamide
-
 Mycobacterium tuberculosis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information Michaelis-Menten kinetics Mycobacterium tuberculosis
0.5
-
 chorismate pH 7.0, 37°C Mycobacterium tuberculosis

Localization

Localization Comment Organism GeneOntology No. Textmining
extracellular the isozyme MtbCM is secreted Mycobacterium tuberculosis
-
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
Chorismate Mycobacterium tuberculosis
-
 Prephenate
-
 ir
Chorismate Mycobacterium tuberculosis ATCC 25618 / H37Rv
-
 Prephenate
-
 ir

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WIB9 secretory isoform
-
Mycobacterium tuberculosis ATCC 25618 / H37Rv P9WIB9 secretory isoform
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
Chorismate
-
 Mycobacterium tuberculosis Prephenate
-
 ir
Chorismate the rearrangement of chorismate to prephenate is strongly exergonic and essentially irreversible in nature Mycobacterium tuberculosis Prephenate
-
 ir
Chorismate
-
 Mycobacterium tuberculosis ATCC 25618 / H37Rv Prephenate
-
 ir
Chorismate the rearrangement of chorismate to prephenate is strongly exergonic and essentially irreversible in nature Mycobacterium tuberculosis ATCC 25618 / H37Rv Prephenate
-
 ir
additional information the isozyme encoded by Rv1885c is characterized as a mono-functional chorismate mutase Mycobacterium tuberculosis ?
-
 ?
additional information the isozyme encoded by Rv1885c is characterized as a mono-functional chorismate mutase Mycobacterium tuberculosis ATCC 25618 / H37Rv ?
-
 ?

Subunits

Subunits Comment Organism
homodimer 2 * 36000 Mycobacterium tuberculosis
More secretory isozyme MtbCM undergoes dimerization mediated through residues (90-119) spanning H3 in both subunits, with the two helices placed anti parallel to each other. The polypeptide consists of eight a-helices H-H8 connected by turns and loop segments Mycobacterium tuberculosis

Synonyms

Synonyms Comment Organism
MtbCM
-
 Mycobacterium tuberculosis
Rv1885c
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Mycobacterium tuberculosis

Temperature Stability [°C]

Temperature Stability Minimum [°C] Temperature Stability Maximum [°C] Comment Organism
60
-
 isozyme MtCM meltig temperature is 48°C, complete inactivation at 60°C Mycobacterium tuberculosis

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
60
-
 chorismate pH 7.0, 37°C 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
0.0057
-
 3-((dihydroxyamino)thio)-4-((3,5-dimethoxyphenethyl)amino)-5-nitrobenzoic acid pH 7.0, 37°C Mycobacterium tuberculosis
0.0177
-
 2-[2-[3-(tert-butoxycarbonyl)-2-phenyl-1,3-thiazolidin-4-yl]ethyl]-4-methylpentanoic acid pH 7.0, 37°C Mycobacterium tuberculosis
0.0211
-
 (2Z)-2-(4-chlorophenyl)-3-[4-(dimethoxymethyl)-2-nitrophenyl]prop-2-enoic acid pH 7.0, 37°C Mycobacterium tuberculosis
0.0288
-
 methyl 4-(methylamino)-3-nitrobenzoate pH 7.0, 37°C Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00101
-
 pH 7.0, 37°C Mycobacterium tuberculosis indoline-2,3-dione
0.0148
-
 pH 7.0, 37°C Mycobacterium tuberculosis ethyl 4-(2-(4-hydroxybut-1-yn-1-yl)phenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate
0.01513
-
 pH 7.0, 37°C Mycobacterium tuberculosis 5-naphthyl-7-propyl-3H-pyrazolo-[4,3-d][1,2,3]triazin-4[5h]-one
0.01563
-
 pH 7.0, 37°C Mycobacterium tuberculosis 3-amino-1-(3-(4-hydroxybut-1-yn-1-yl)phenyl)-1H-benzol[f]chromene-2-carbonitril
0.0197
-
 pH 7.0, 37°C Mycobacterium tuberculosis 2-chloro-3-(5,6-difluoro-1H-indol-3-yl)quinoxaline
0.0198
-
 pH 7.0, 37°C Mycobacterium tuberculosis 3-(3-methoxyphenyl)-5,6,7,8-tetrahydrobenzo[b]thieno[2,3d]pyrimidin-4[3H]-one
0.0239
-
 pH 7.0, 37°C Mycobacterium tuberculosis 2-chloro-4-(ethoxycarbonyl)-1-hydroxy-6-methylquinolin-1-ium

General Information

General Information Comment Organism
evolution isozyme MtbCM belongs to the ?AroQ/AroQc family. The family members exhibit sequence similarity only in the N-terminal moiety, and lack a catalytically crucial and conserved arginine residue in helix H1. The proteins contain a catalytic site which is formed within a single protomer and lacks regulatory domain Mycobacterium tuberculosis
malfunction the inhibition of secretory isozyme MtbCM may hinder the supply of nutrients to the organism Mycobacterium tuberculosis
metabolism Mycobacterium tuberculosis chorismate mutase (MtbCM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway which forms the essential amino acids, phenylalanine and tyrosine Mycobacterium tuberculosis
physiological function Mycobacterium tuberculosis chorismate mutase (MtbCM) catalyzes the rearrangement of chorismate to prephenate in the shikimate biosynthetic pathway which forms the essential amino acids, phenylalanine and tyrosine. The secretory isozyme MtbCM (encoded by gene Rv1885c) is assumed to play a key role in pathogenesis of tuberculosis. Isozyme MtbCM is independent of regulation Mycobacterium tuberculosis

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
120
-
 chorismate pH 7.0, 37°C Mycobacterium tuberculosis