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

BRENDA support

Literature summary for 2.1.1.228 extracted from

  • Sakaguchi, R.; Lahoud, G.; Christian, T.; Gamper, H.; Hou, Y.M.
    A divalent metal ion-dependent N1-methyl transfer to G37-tRNA (2014), Chem. Biol., 21, 1351-1360.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development TrmD has potential as a drug target Escherichia coli

KM Value [mM]

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

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/ Products (Substrates)

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

Organism UniProt Comment Textmining
Escherichia coli
-
gene trmD
-

Reaction

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 and Products (Substrate)

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

Subunits Comment Organism
dimer
-
Escherichia coli

Synonyms

Synonyms Comment Organism
TrmD
-
Escherichia coli

Cofactor

Cofactor Comment Organism Structure
S-adenosyl-L-methionine dependent on Escherichia coli

General Information

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