Application | Comment | Organism |
---|---|---|
drug development | the enzyme is an attractive target for development of antibacterial drugs against Mycobacterium abscessus, which possesses both intrinsic and acquired resistance to available antibiotics and is therefore currently difficult or sometimes impossible to treat | Mycobacteroides abscessus |
Cloned (Comment) | Organism |
---|---|
gene trmD, recombinant expression of His-tagged enzyme from AVA0421 plasmid with an N-His-3C protease site in Escherichia coli strain BL21(DE3) | Mycobacteroides abscessus |
Crystallization (Comment) | Organism |
---|---|
purified recombinant detagged enzyme TrmD as apoenzyme and in complex with S-adenosyl-L-methionine, sitting drop vapour diffusion method, for the apo-TrmD crystals, 0.001 ml of 20 mg/ml protein in storage buffer containing 25 mM HEPES, pH 7.5, 500 mM NaCl, and 5% glycerol are mixed with 0.001 ml of reservoir solution containing 0.08 mM sodium cacodylate pH 6.5-7.0, 1-2 M and ammonium sulfate, and equilibrated against 0.25 ml of reservoir solution, the apo crystals formed are allowed to soak in a 0.004 ml drop containing reservoir solution and 10 mM ligand (in DMSO) and equilibrated against 0.7 ml of the corresponding reservoir solution overnight at 19°C in hanging drop vapor diffusion plates, X-ray diffraction structure determination and analysis at 1.67 A resolution, molecular replacement using the solved Mab TrmD apo structure (PDB code 6NVR) as a search model | Mycobacteroides abscessus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
1H-indol-4-ylboronic acid | - |
Mycobacteroides abscessus | |
1H-indol-5-ylboronic acid | - |
Mycobacteroides abscessus | |
1H-indole-4-carboxylic acid | - |
Mycobacteroides abscessus | |
2-((6-(3-amino-1H-pyrazol-5-yl)-1H-indol-1-yl)methyl)-benzamide | - |
Mycobacteroides abscessus | |
2-((6-(3-amino-1H-pyrazol-5-yl)-1H-indol-1-yl)methyl)-benzonitrile | - |
Mycobacteroides abscessus | |
3-(2-methoxy-2-oxoethoxy)benzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-(pyridin-2-ylmethoxy)benzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-amino-5-(1-((1-methylpiperidin-2-yl)methyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-((1-methylpiperidin-3-yl)methyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-((2-hydroxypyridin-3-yl)methyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-((6-hydroxypyridin-3-yl)methyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-(4-((4-isopropylpiperazin-1-yl)methyl)-benzyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-(4-(morpholinomethyl)benzyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-(4-(piperidin-1-ylmethyl)benzyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-(pyridin-3-ylmethyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-(pyridin-4-ylmethyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-(quinolin-4-ylmethyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1-benzyl-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-(3-chloro-1-(pyridin-3-ylmethyl)-1H-indol-6-yl)-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-[1-([4-[(4-methylpiperazin-1-yl)methyl]phenyl]methyl)-1H-indol-6-yl]-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-[1-([4-[(pyrrolidin-1-yl)methyl]phenyl]methyl)-1H-indol-6-yl]-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-[1-([5-[(pyrrolidin-1-yl)methyl]pyridin-2-yl]methyl)-1H-indol-6-yl]-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-amino-5-[1-[(pyridin-2-yl)methyl]-1H-indol-6-yl]-1H-pyrazole-4-carbonitrile | - |
Mycobacteroides abscessus | |
3-cyanobenzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-ethoxybenzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-methoxy-5-(pyridin-3-yl)benzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-methoxy-5-(pyridin-3-ylmethyl)benzyl-1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-methoxy-5-(pyrrolidin-1-yl)benzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-methoxybenzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
3-phenethoxybenzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
4-(methoxycarbonyl)benzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
4-methyl-5-(1-(4-(pyrrolidin-1-ylmethyl)benzyl)-1H-indol-6-yl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
4-nitrobenzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
5-(1-(3-methoxybenzyl)-1H-indol-6-yl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-(1-(4-(piperidin-1-ylmethyl)benzyl)-1H-indol-6-yl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-(1-(4-methoxybenzyl)-1H-indol-6-yl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-(1-benzyl-1H-indol-6-yl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-(1H-indol-6-yl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-(3-methoxyphenyl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-(4-methoxyphenyl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-(4-methylphenyl)-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-phenyl-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-[1-([4-[(pyrrolidin-1-yl)methyl]phenyl]methyl)-1H-indol-6-yl]-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
5-[1-[(pyridin-2-yl)methyl]-1H-indol-6-yl]-1H-pyrazol-3-amine | - |
Mycobacteroides abscessus | |
benzyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
ethyl 1-(3-(3-(((1H-pyrazole-4-carbonyl)oxy)methyl)-5-methoxyphenyl)prop-2-yn-1-yl)-1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
ethyl 1H-pyrazole-4-carboxylate | - |
Mycobacteroides abscessus | |
additional information | development of inhibitors against Mycobacterium abscessus tRNA (m1G37) methyltransferase (TrmD) using fragment-based approaches, inhibitor screening, overview. Determination of inhibitor thermodynamics and binding kinetics | Mycobacteroides abscessus | |
N-ethyl-1H-pyrazole-4-carboxamide | - |
Mycobacteroides abscessus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
S-adenosyl-L-methionine + guanine37 in tRNA | Mycobacteroides abscessus | - |
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacteroides abscessus | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, tag cleavage through 3C protease, another step of nickel affinity chromatography, followed by gel filtration | Mycobacteroides abscessus |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
S-adenosyl-L-methionine + guanine37 in tRNA | - |
Mycobacteroides abscessus | S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | crystal structure analysis | Mycobacteroides abscessus |
Synonyms | Comment | Organism |
---|---|---|
TrmD | - |
Mycobacteroides abscessus |
tRNA (m1G37) methyltransferase | - |
Mycobacteroides abscessus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
S-adenosyl-L-methionine | - |
Mycobacteroides abscessus |
General Information | Comment | Organism |
---|---|---|
evolution | tRNA (m1G37) methyltransferase (TrmD), a member of the SpoU-TrmD (SPOUT) RNA methyltransferase family | Mycobacteroides abscessus |
physiological function | TrmD catalyzes the transfer of a methyl group from S-adenosyl methionine (SAM) to the N1 position of guanosine 37 in bacterial tRNA when preceded by another guanosine in the sequence. The addition of this marker immediately adjacent to the anticodon acts to improve reading frame maintenance on the ribosome, preventing frameshift errors that would result in truncated and inactive peptides. TrmD is essential for growth in a range of bacterial species from Staphylococcus aureus and Pseudomonas aeruginosa to mycobacteria, including Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mab) | Mycobacteroides abscessus |