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 (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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Bacillus subtilis | P13956 | expressed in Escherichia coli DH5alpha cells | - |
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 20732090 and 26382651) | Bacillus subtilis | 2 S-adenosyl-L-homocysteine + N6-dimethyladenine2085 in 23S rRNA | - |
? |
Synonyms | Comment | Organism |
---|---|---|
ErmC methyltransferase | - |
Bacillus subtilis |
ErmC' | - |
Bacillus subtilis |
ErmC' MTase | - |
Bacillus subtilis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
25 | - |
assay at | Bacillus subtilis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Bacillus subtilis |
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 |