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Literature summary for 5.1.1.3 extracted from

  • Malapati, P.; Krishna, V.S.; Nallangi, R.; Srilakshmi, R.R.; Sriram, D.
    Identification and development of benzoxazole derivatives as novel bacterial glutamate racemase inhibitors (2018), Eur. J. Med. Chem., 145, 23-34 .
    View publication on PubMed
Search for more literature for 5.1.1.3

Cloned(Commentary)

Cloned (Comment) Organism
gene murI, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3) Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-(4-nitrophenyl)thiourea
-
 Mycobacterium tuberculosis
1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-(p-tolyl)thiourea
-
 Mycobacterium tuberculosis
1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-phenylthiourea
-
 Mycobacterium tuberculosis
1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-phenylurea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-chlorophenyl)thiourea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-chlorophenyl)urea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-fluorophenyl)thiourea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-fluorophenyl)urea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-methoxyphenyl)urea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-nitrophenyl)thiourea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-nitrophenyl)urea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(p-tolyl)thiourea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(p-tolyl)urea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-benzylthiourea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-benzylurea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-isopropylurea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-phenylthiourea
-
 Mycobacterium tuberculosis
1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-phenylurea
-
 Mycobacterium tuberculosis
1-(4-chlorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)thiourea Binding pose and the interaction pattern of the compound, non-competitive inhibition Mycobacterium tuberculosis
1-(4-chlorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)urea
-
 Mycobacterium tuberculosis
1-(4-fluorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)thiourea
-
 Mycobacterium tuberculosis
1-(4-fluorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)urea
-
 Mycobacterium tuberculosis
1-(4-methoxyphenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)urea
-
 Mycobacterium tuberculosis
1-benzyl-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)thiourea
-
 Mycobacterium tuberculosis
3-(5-methylbenzo[d]oxazol-2-yl)aniline
-
 Mycobacterium tuberculosis
3-(benzo[d]oxazol-2-yl)aniline
-
 Mycobacterium tuberculosis
additional information development of a class of Mycobacterium tuberculosis (Mtb) inhibitors by exploring the pharmaceutically underexploited enzyme targets which are majorly involved in cell wall biosynthesis of mycobacteria, compoud library screening using a thermal shift assay. Identification of two lead compounds, optimization and expansion result in twenty four compounds. Molecular docking and dynamic studies using the D-glutamate bound glutamate racemase structures of Mycobacterium tuberculosis (PDB ID 5HJ7) and Bacillus subtilis (PDB ID 1ZUW), simulations and modeling, overview. The compounds are also tested on their cytotoxicity and in a Myconacterium tuberculosis biofilm assay, activity profile of compounds in nutrient starved stress model, overview Mycobacterium tuberculosis
N-benzyl-N'-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]urea
-
 Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
L-glutamate Mycobacterium tuberculosis
-
 D-glutamate
-
 r
L-glutamate Mycobacterium tuberculosis ATCC 25618 / H37Rv
-
 D-glutamate
-
 r

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WPW9
-
-
Mycobacterium tuberculosis ATCC 25618 / H37Rv P9WPW9
-
-

Purification (Commentary)

Purification (Comment) Organism
gene murI, recombinant expression of His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography Mycobacterium tuberculosis

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-glutamate
-
 Mycobacterium tuberculosis D-glutamate
-
 r
L-glutamate
-
 Mycobacterium tuberculosis ATCC 25618 / H37Rv D-glutamate
-
 r

Synonyms

Synonyms Comment Organism
MurI
-
 Mycobacterium tuberculosis

Temperature Optimum [°C]

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

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8
-
 assay at Mycobacterium tuberculosis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0011
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-fluorophenyl)thiourea
0.0013
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-benzylthiourea
0.00182
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-fluorophenyl)urea
0.0044
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-nitrophenyl)thiourea
0.00625
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis N-benzyl-N'-[3-(5-methyl-1,3-benzoxazol-2-yl)phenyl]urea
0.0068
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-(4-nitrophenyl)thiourea
0.007
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 3-(5-methylbenzo[d]oxazol-2-yl)aniline
0.00712
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-isopropylurea
0.00835
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(p-tolyl)urea
0.0085
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(4-fluorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)urea
0.0088
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-phenylthiourea
0.0115
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-chlorophenyl)urea
0.0228
-
 pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(4-fluorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)thiourea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-(p-tolyl)thiourea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)-3-phenylurea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-chlorophenyl)thiourea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-methoxyphenyl)urea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(4-nitrophenyl)urea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-(p-tolyl)thiourea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-benzylurea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-phenylthiourea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(3-(benzo[d]oxazol-2-yl)phenyl)-3-phenylurea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(4-chlorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)thiourea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(4-chlorophenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)urea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-(4-methoxyphenyl)-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)urea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 1-benzyl-3-(3-(5-methylbenzo[d]oxazol-2-yl)phenyl)thiourea
0.025
-
 above, pH 8.0, 37°C, recombinant enzyme Mycobacterium tuberculosis 3-(benzo[d]oxazol-2-yl)aniline

General Information

General Information Comment Organism
metabolism glutamate racemase racemizes D-glutamate from L-glutamate, a key step in peptidoglycan synthesis Mycobacterium tuberculosis
physiological function glutamate racemase racemizes D-glutamate from L-glutamate, a key step in peptidoglycan synthesis Mycobacterium tuberculosis