Application | Comment | Organism |
---|---|---|
drug development | TrmD has potential as a drug target | Escherichia coli |
KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
---|---|---|---|---|---|
additional information | - |
additional information | measurement of the pre-steady-state rate constant of methyl transfer of TrmD, a proton abstraction step is rate limiting, steady-state kinetics | Escherichia coli |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Ca2+ | can partially substitute for Mg2+ | Escherichia coli | |
Mg2+ | dependent on, one Mg2+ per enzyme dimer. Mg2+ is not involved in substrate binding, but in promoting methyl transfer. Mg2+ promotes methyl transfer of TrmD not by stabilizing the binding of tRNA or AdoMet, but by accelerating the chemical rate. Mg2+ interacts with the O6 of G37-tRNA | Escherichia coli | |
Mn2+ | can partially substitute for Mg2+ | Escherichia coli | |
additional information | bacterial enzyme TrmD is strongly dependent on divalent metal ions and Mg2+ is the most physiologically relevant. Divalent metal ions are recruited to stabilize the developing negative charge at the 6-position of G37, while also favoring the abstraction of the N1 proton to activate the nucleophile. Co2+ is unable to substitute for Mg2+, replacement of Mg2+ with Co2+ decreases methyl transfer, substitution of the 6-oxygen (O6) of G37 with 6-thio (S6) in the substrate tRNA restores the activity. Kinetics of metal ions in the reaction,overview | Escherichia coli |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
S-adenosyl-L-methionine + guanine37 in tRNA | Escherichia coli | - |
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | - |
gene trmD | - |
Reaction | Comment | Organism | Reaction ID |
---|---|---|---|
S-adenosyl-L-methionine + guanine37 in tRNA = S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA | catalytic mechanism in which the role of Mg2+ is to help to increase the nucleophilicity of N1 of G37 and stabilize the negative developing charge on O6 during attack on the methyl sulfonium of S-adenosyl-L-methionine. Substrate binding to EcTrmD is in rapid equilibrium to form the enzyme-tRNA-S-adenosyl-L-methionine complex, a proton abstraction step is rate limiting in methyl transfer | Escherichia coli |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
S-adenosyl-L-methionine + guanine37 in tRNA | - |
Escherichia coli | S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA | - |
? | |
S-adenosyl-L-methionine + guanine37 in tRNA | the pH-activity profile indicates one proton transfer during the TrmD reaction | Escherichia coli | S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA | - |
? |
Subunits | Comment | Organism |
---|---|---|
dimer | - |
Escherichia coli |
Synonyms | Comment | Organism |
---|---|---|
TrmD | - |
Escherichia coli |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
S-adenosyl-L-methionine | dependent on | Escherichia coli |
General Information | Comment | Organism |
---|---|---|
evolution | the dedication of Mg2+ to rate enhancement separates TrmD from O- and N6-methyl transferases. TrmD shows the topologically knotted protein fold | Escherichia coli |
physiological function | S-adenosyl-L-methionine-dependent methyl transfer in one of the most crucial posttranscriptional modifications to tRNA | Escherichia coli |