Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.1.1.184 extracted from

  • Feder, M.; Purta, E.; Koscinski, L.; Ebrilo, S.; Vlahovicek, G.; Bujnicki, J.
    Virtual screening and experimental verification to identify potential inhibitors of the ErmC methyltransferase responsible for bacterial resistance against macrolide antibiotics (2008), ChemMedChem, 3, 316-322.
    View publication on PubMed

Application

Application Comment Organism
medicine ErmC' catalyzes S-adenosyl-L-methionine-dependent modification of a specific adenine residue in bacterial 23S rRNA, thereby conferring resistance to clinically important macrolide, lincosamide, and streptogramin B antibiotics. The crystal structure of ErmC’ methyltransferase is used as a target for structure-based virtual screening of a database composed of 58679 lead-like compounds. Among 77 compounds selected for experimental validation (63 predicted to bind to the catalytic pocket and 14 compounds predicted to bind to the putative RNA bindingsite), several novel inhibitors are found that decrease the minimal inhibitory concentration of a macrolide antibiotic erythromycin toward an Escherichia coli strain that constitutively expresses ErmC'. Analysis of docking models of the identified inhibitors suggests a novel strategy to develop potent and clinically useful inhibitors Bacillus subtilis

Crystallization (Commentary)

Crystallization (Comment) Organism
the crystal structure of ErmC’ methyltransferase is used as a target for structure-based virtual screening of a database composed of 58679 lead-like compounds. Analysis of docking models of the identified inhibitors suggests a novel strategy to develop potent and clinically useful inhibitors Bacillus subtilis

Inhibitors

Inhibitors Comment Organism Structure
2-([[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl][3-(1H-imidazol-1-yl)propyl]amino]methyl)-1H-isoindole-1,3(2H)-dione i.e. PD00556 Bacillus subtilis
4-methyl-2,6-di[(4-methylphenyl)thio]nicotinonitrile i.e. RF00667 Bacillus subtilis
additional information the crystal structure of ErmC’ methyltransferase is used as a target for structure-based virtual screening of a database composed of 58679 lead-like compounds. Among 77 compounds selected for experimental validation (63 predicted to bind to the catalytic pocket and 14 compounds predicted to bind to the putative RNA binding site), several novel inhibitors are found that decrease the minimal inhibitory concentration of a macrolide antibiotic erythromycin toward an Escherichia coli strain that constitutively expresses ErmC'. Analysis of docking models of the identified inhibitors suggests a novel strategy to develop potent and clinically useful inhibitors Bacillus subtilis
nicotinaldehyde-N-[3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl]hydrazone i.e. HTS12610 Bacillus subtilis

Organism

Organism UniProt Comment Textmining
Bacillus subtilis P13956 expressed in Escherichia coli DH5alpha cells
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2 S-adenosyl-L-methionine + adenine2085 in 23S rRNA synthetic 32-nt RNA oligonucleotide (5’-GCGACGGACGGA2085AAGACCCCUAUCCGUCGCG-3’, hairpin structure) designed to mimic the adenine loop in domain V of Bacillus subtilis 23S rRNA (residues 2073–2090 and 2638–2651) Bacillus subtilis 2 S-adenosyl-L-homocysteine + N6-dimethyladenine2085 in 23S rRNA
-
?

Synonyms

Synonyms Comment Organism
ErmC methyltransferase
-
Bacillus subtilis
ErmC'
-
Bacillus subtilis
ErmC' MTase
-
Bacillus subtilis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
assay at Bacillus subtilis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Bacillus subtilis

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.18
-
pH 7.5, 25°C Bacillus subtilis 4-methyl-2,6-di[(4-methylphenyl)thio]nicotinonitrile
0.25
-
pH 7.5, 25°C Bacillus subtilis nicotinaldehyde-N-[3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-7-yl]hydrazone
0.3
-
pH 7.5, 25°C Bacillus subtilis 2-([[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl][3-(1H-imidazol-1-yl)propyl]amino]methyl)-1H-isoindole-1,3(2H)-dione