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Literature summary for 2.7.7.60 extracted from

  • Haymond, A.; Dowdy, T.; Johny, C.; Johnson, C.; Ball, H.; Dailey, A.; Schweibenz, B.; Villarroel, K.; Young, R.; Mantooth, C.J.; Patel, T.; Bases, J.; Dowd, C.S.; Couch, R.D.
    A high-throughput screening campaign to identify inhibitors of DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD) (2018), Anal. Biochem., 542, 63-75 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 2.7.7.60

Application

Application Comment Organism
drug development the methyl erythritol phosphate (MEP) pathway, including enzyme MEP cytidylyltransferase (IspD), represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues Escherichia coli
drug development the methyl erythritol phosphate (MEP) pathway, including enzyme MEP cytidylyltransferase (IspD), represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues Francisella tularensis subsp. novicida

Cloned(Commentary)

Cloned (Comment) Organism
gene ispD, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Codon Plus (DE3)-RIL Escherichia coli
gene ispD, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21 Codon Plus (DE3)-RIL Francisella tularensis subsp. novicida

Inhibitors

Inhibitors Comment Organism Structure
6-hydroxy-DL-DOPA
-
 Francisella tularensis subsp. novicida
aurintricarboxylic acid
-
 Francisella tularensis subsp. novicida
chelerythrine
-
 Francisella tularensis subsp. novicida
dequalinium
-
 Francisella tularensis subsp. novicida
fosmidomycin
-
 Escherichia coli
fosmidomycin
-
 Francisella tularensis subsp. novicida
MMV008138
-
 Escherichia coli
MMV008138
-
 Francisella tularensis subsp. novicida
additional information high-throughput screening to identify inhibitors of MEP cytidylyltransferase (IspD) Escherichia coli
additional information bench-scale high-throughput screening to identify inhibitors of MEP cytidylyltransferase (IspD) using purified, recombinant IspD, a commercially available 1280 compound molecular library, and a 150 sample, in-house prepared, natural product extract library. The enzyme activity is not affected by 0.01% Triton X-100, but inhibition is attenuated in the presence of Triton X-100 for all inhibitors, except 6-hydroxy-DL-DOPA Francisella tularensis subsp. novicida
quercetin quercetin is retained as a lead molecule for inhibition of IspD, 96% inhibition at 0.1 mM Francisella tularensis subsp. novicida
U-74389G maleate
-
 Francisella tularensis subsp. novicida

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Escherichia coli
Mg2+ required Francisella tularensis subsp. novicida

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
CTP + 2-C-methyl-D-erythritol 4-phosphate Escherichia coli
-
 diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
-
 ?
CTP + 2-C-methyl-D-erythritol 4-phosphate Francisella tularensis subsp. novicida
-
 diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
-
 ?
CTP + 2-C-methyl-D-erythritol 4-phosphate Francisella tularensis subsp. novicida Utah 112
-
 diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
-
 ?

Organism

Organism UniProt Comment Textmining
Escherichia coli Q46893
-
-
Francisella tularensis subsp. novicida A0Q5K1
-
-
Francisella tularensis subsp. novicida Utah 112 A0Q5K1
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged enzyme from Escherichia coli strain BL21 Codon Plus (DE3)-RIL by metal affinity chromatography and ultrafiltration Escherichia coli
recombinant His-tagged enzyme from Escherichia coli strain BL21 Codon Plus (DE3)-RIL by metal affinity chromatography and ultrafiltration Francisella tularensis subsp. novicida

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
CTP + 2-C-methyl-D-erythritol 4-phosphate
-
 Escherichia coli diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
-
 ?
CTP + 2-C-methyl-D-erythritol 4-phosphate
-
 Francisella tularensis subsp. novicida diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
-
 ?
CTP + 2-C-methyl-D-erythritol 4-phosphate
-
 Francisella tularensis subsp. novicida Utah 112 diphosphate + 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol
-
 ?

Synonyms

Synonyms Comment Organism
EcIspD
-
 Escherichia coli
FtIspD
-
 Francisella tularensis subsp. novicida
IspD
-
 Escherichia coli
IspD
-
 Francisella tularensis subsp. novicida
MEP cytidylyltransferase
-
 Escherichia coli
MEP cytidylyltransferase
-
 Francisella tularensis subsp. novicida

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Escherichia coli
37
-
 assay at Francisella tularensis subsp. novicida

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.2
-
 assay at Escherichia coli
8.2
-
 assay at Francisella tularensis subsp. novicida

General Information

General Information Comment Organism
metabolism the MEP cytidylyltransferase, or IspD catalyzes the second committed step of the methyl erythritol phosphate (MEP) pathway. The MEP pathway is essential for the production of isoprenoids Escherichia coli
metabolism the MEP cytidylyltransferase, or IspD catalyzes the second committed step of the methyl erythritol phosphate (MEP) pathway. The MEP pathway is essential for the production of isoprenoids Francisella tularensis subsp. novicida