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Literature summary extracted from

  • Hou, Y.; Matsubara, R.; Takase, R.; Masuda, I.; Sulkowska, J.
    TrmD A methyl transferase for tRNA methylation with m1G37 (2017), Enzymes, 41, 89-115 .
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.1.1.228 drug development TrmD is ranked as a high-priority antimicrobial target Aquifex aeolicus
2.1.1.228 drug development TrmD is ranked as a high-priority antimicrobial target Escherichia coli
2.1.1.228 drug development TrmD is ranked as a high-priority antimicrobial target Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 drug development TrmD is ranked as a high-priority antimicrobial target Haemophilus influenzae

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.1.1.228 gene trmD, sequence comparisons Aquifex aeolicus
2.1.1.228 gene trmD, sequence comparisons Escherichia coli
2.1.1.228 gene trmD, sequence comparisons Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 gene trmD, sequence comparisons Haemophilus influenzae

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.1.1.228 Ca2+ can substitute Mg2+ to lesser extent Aquifex aeolicus
2.1.1.228 Ca2+ can substitute Mg2+ to lesser extent Escherichia coli
2.1.1.228 Ca2+ can substitute Mg2+ to lesser extent Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 Ca2+ can substitute Mg2+ to lesser extent Haemophilus influenzae
2.1.1.228 Mg2+ methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics Aquifex aeolicus
2.1.1.228 Mg2+ methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics Escherichia coli
2.1.1.228 Mg2+ methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 Mg2+ methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics Haemophilus influenzae
2.1.1.228 additional information in addition to Mg2+, TrmD can also use Ca2+ and Mn2+ as an active ion, but not Ni2+ or Co2+. The single Mg2+ required for methyl transfer is involved in the abstraction of the N1 proton from G37-tRNA, which is likely the rate-limiting step of the TrmD-catalyzed methyl transfer Aquifex aeolicus
2.1.1.228 additional information in addition to Mg2+, TrmD can also use Ca2+ and Mn2+ as an active ion, but not Ni2+ or Co2+. The single Mg2+ required for methyl transfer is involved in the abstraction of the N1 proton from G37-tRNA, which is likely the rate-limiting step of the TrmD-catalyzed methyl transfer Escherichia coli
2.1.1.228 additional information in addition to Mg2+, TrmD can also use Ca2+ and Mn2+ as an active ion, but not Ni2+ or Co2+. The single Mg2+ required for methyl transfer is involved in the abstraction of the N1 proton from G37-tRNA, which is likely the rate-limiting step of the TrmD-catalyzed methyl transfer Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 additional information in addition to Mg2+, TrmD can also use Ca2+ and Mn2+ as an active ion, but not Ni2+ or Co2+. The single Mg2+ required for methyl transfer is involved in the abstraction of the N1 proton from G37-tRNA, which is likely the rate-limiting step of the TrmD-catalyzed methyl transfer Haemophilus influenzae
2.1.1.228 Ni2+ can substitute Mg2+ to lesser extent Aquifex aeolicus
2.1.1.228 Ni2+ can substitute Mg2+ to lesser extent Escherichia coli
2.1.1.228 Ni2+ can substitute Mg2+ to lesser extent Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 Ni2+ can substitute Mg2+ to lesser extent Haemophilus influenzae

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.1.1.228 additional information Aquifex aeolicus TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon ?
-
-
2.1.1.228 additional information Escherichia coli TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon ?
-
-
2.1.1.228 additional information Salmonella enterica subsp. enterica serovar Typhimurium TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon ?
-
-
2.1.1.228 additional information Haemophilus influenzae TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon ?
-
-
2.1.1.228 additional information Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412 TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon ?
-
-
2.1.1.228 additional information Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720 TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon ?
-
-
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA Aquifex aeolicus
-
 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA Escherichia coli
-
 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA Salmonella enterica subsp. enterica serovar Typhimurium
-
 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA Haemophilus influenzae
-
 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412
-
 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720
-
 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.1.1.228 Aquifex aeolicus O67463
-
-
2.1.1.228 Escherichia coli P0A873
-
-
2.1.1.228 Haemophilus influenzae A0A0D0GZF5
-
-
2.1.1.228 Salmonella enterica subsp. enterica serovar Typhimurium P36245
-
-
2.1.1.228 Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720 P36245
-
-
2.1.1.228 Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412 P36245
-
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.1.1.228 additional information TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon Aquifex aeolicus ?
-
-
2.1.1.228 additional information TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon Escherichia coli ?
-
-
2.1.1.228 additional information TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon Salmonella enterica subsp. enterica serovar Typhimurium ?
-
-
2.1.1.228 additional information TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon Haemophilus influenzae ?
-
-
2.1.1.228 additional information TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412 ?
-
-
2.1.1.228 additional information TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720 ?
-
-
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA
-
 Aquifex aeolicus S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA
-
 Escherichia coli S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA
-
 Salmonella enterica subsp. enterica serovar Typhimurium S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA
-
 Haemophilus influenzae S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA
-
 Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?
2.1.1.228 S-adenosyl-L-methionine + guanine37 in tRNA
-
 Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720 S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
 ?

Subunits

EC Number Subunits Comment Organism
2.1.1.228 dimer TrmD is an obligated homodimer that places each active site at the dimer interface Aquifex aeolicus
2.1.1.228 dimer TrmD is an obligated homodimer that places each active site at the dimer interface Escherichia coli
2.1.1.228 dimer TrmD is an obligated homodimer that places each active site at the dimer interface Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 dimer TrmD is an obligated homodimer that places each active site at the dimer interface Haemophilus influenzae
2.1.1.228 More in both monomeric chains of TrmD, AdoMet is bound in the N-terminal domain to the deep cleft of a trefoil knot fold, which is a topological knot that involves three crossings of the protein backbone through a loop, the trefoil knot in TrmD is shown to be required for methyl transfer, knot structure and function, overview. The trefoil knot of TrmD is required for the catalytic mechanism in three ways Escherichia coli
2.1.1.228 More in both monomeric chains of TrmD, AdoMet is bound in the N-terminal domain to the deep cleft of a trefoil knot fold, which is a topological knot that involves three crossings of the protein backbone through a loop, the trefoil knot in TrmD is shown to be required for methyl transfer, knot structure and function, overview. The trefoil knot of TrmD is required for the catalytic mechanism in three ways Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 More in both monomeric chains of TrmD, AdoMet is bound in the N-terminal domain to the deep cleft of a trefoil knot fold, which is a topological knot that involves three crossings of the protein backbone through a loop, the trefoil knot in TrmD is shown to be required for methyl transfer, knot structure and function, overview. The trefoil knot of TrmD is required for the catalytic mechanism in three ways Haemophilus influenzae
2.1.1.228 More without the knot, as found in the crystal structure of Aquifex aeolicus TrmD, AdoMet cannot bend and can only exist in the open shape. Without being in the bent shape, AdoMet is be positioned in a spatial geometry incompatible with the position of the G37 base and unfavorable for methyl transfer. The m1G37 methylation by TrmD does not need any other prior modification, aminoacylation, or even CCA addition to tRNA Aquifex aeolicus

Synonyms

EC Number Synonyms Comment Organism
2.1.1.228 EcTrmD
-
 Escherichia coli
2.1.1.228 HiTrmD
-
 Haemophilus influenzae
2.1.1.228 TrmD
-
 Aquifex aeolicus
2.1.1.228 TrmD
-
 Escherichia coli
2.1.1.228 TrmD
-
 Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 TrmD
-
 Haemophilus influenzae

Cofactor

EC Number Cofactor Comment Organism Structure
2.1.1.228 S-adenosyl-L-methionine
-
 Aquifex aeolicus
2.1.1.228 S-adenosyl-L-methionine
-
 Escherichia coli
2.1.1.228 S-adenosyl-L-methionine
-
 Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 S-adenosyl-L-methionine
-
 Haemophilus influenzae

General Information

EC Number General Information Comment Organism
2.1.1.228 evolution TrmD is broadly conserved in sequence and structure among bacterial species, in both Gram (+) and Gram (-), but it is absent from the eukaryotic and archaeal domains. TrmD is strongly conserved in sequence among evolutionarily diverse bacterial species Aquifex aeolicus
2.1.1.228 evolution TrmD is broadly conserved in sequence and structure among bacterial species, in both Gram (+) and Gram (-), but it is absent from the eukaryotic and archaeal domains. TrmD is strongly conserved in sequence among evolutionarily diverse bacterial species Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 evolution TrmD is broadly conserved in sequence and structure among bacterial species, in both Gram (+) and Gram (-), but it is absent from the eukaryotic and archaeal domains. TrmD is strongly conserved in sequence among evolutionarily diverse bacterial species. In all of the available structures of the TrmD dimer, each monomeric chain is made up of three distinct domains: an N-terminal domain (residues 1-160 in HiTrmD and EcTrmD) for binding AdoMet, a C-terminal domain for binding tRNA (residues 169-246), and a flexible linker in between (residues 161-168) Escherichia coli
2.1.1.228 evolution TrmD is broadly conserved in sequence and structure among bacterial species, in both Gram (+) and Gram (-), but it is absent from the eukaryotic and archaeal domains. TrmD is strongly conserved in sequence among evolutionarily diverse bacterial species. In all of the available structures of the TrmD dimer, each monomeric chain is made up of three distinct domains: an N-terminal domain (residues 1-160 in HiTrmD and EcTrmD) for binding AdoMet, a C-terminal domain for binding tRNA (residues 169-246), and a flexible linker in between (residues 161-168) Haemophilus influenzae
2.1.1.228 malfunction mutations in the TrmD knot block this intramolecular signaling and decrease the synthesis of m1G37-tRNA, prompting ribosomes to +1-frameshifts and premature termination of protein synthesis. Ribosome frameshifting in the absence of TrmD, overview Aquifex aeolicus
2.1.1.228 malfunction mutations in the TrmD knot block this intramolecular signaling and decrease the synthesis of m1G37-tRNA, prompting ribosomes to +1-frameshifts and premature termination of protein synthesis. Ribosome frameshifting in the absence of TrmD, overview Escherichia coli
2.1.1.228 malfunction mutations in the TrmD knot block this intramolecular signaling and decrease the synthesis of m1G37-tRNA, prompting ribosomes to +1-frameshifts and premature termination of protein synthesis. Ribosome frameshifting in the absence of TrmD, overview Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 malfunction mutations in the TrmD knot block this intramolecular signaling and decrease the synthesis of m1G37-tRNA, prompting ribosomes to +1-frameshifts and premature termination of protein synthesis. Ribosome frameshifting in the absence of TrmD, overview Haemophilus influenzae
2.1.1.228 additional information the m1G37 methylation by TrmD does not need any other prior modification, aminoacylation, or even CCA addition to tRNA. Transient nature of Mg2+ is consistent with the proposed catalytic mechanism involving G37-tRNA. In this mechanism, D169 is the general base to abstract the N1 proton from G37, while the deprotonation is accompanied by developing electron density on the O6 of G37. The developing negative charge on O6 of G37 is stabilized through coordination with Mg2+ and by hydrogen-bond interaction with the side chain of R154. The charge stabilization of O6 in turn facilitates Mg2+ to coordinate with the general base D169 and to help it to align more properly for proton abstraction. The activated N1 nucleophile is then poised for nucleophilic attack on the sulfonium center of AdoMet, resulting in synthesis of m1G37-tRNA and release of AdoHcy. The rate-limiting step is assigned to the action of D169, rather than to the protonation of the leaving group, due to the importance of D169 and the increase of activity as the proton concentration is lowered Aquifex aeolicus
2.1.1.228 additional information the m1G37 methylation by TrmD does not need any other prior modification, aminoacylation, or even CCA addition to tRNA. Transient nature of Mg2+ is consistent with the proposed catalytic mechanism involving G37-tRNA. In this mechanism, D169 is the general base to abstract the N1 proton from G37, while the deprotonation is accompanied by developing electron density on the O6 of G37. The developing negative charge on O6 of G37 is stabilized through coordination with Mg2+ and by hydrogen-bond interaction with the side chain of R154. The charge stabilization of O6 in turn facilitates Mg2+ to coordinate with the general base D169 and to help it to align more properly for proton abstraction. The activated N1 nucleophile is then poised for nucleophilic attack on the sulfonium center of AdoMet, resulting in synthesis of m1G37-tRNA and release of AdoHcy. The rate-limiting step is assigned to the action of D169, rather than to the protonation of the leaving group, due to the importance of D169 and the increase of activity as the proton concentration is lowered Escherichia coli
2.1.1.228 additional information the m1G37 methylation by TrmD does not need any other prior modification, aminoacylation, or even CCA addition to tRNA. Transient nature of Mg2+ is consistent with the proposed catalytic mechanism involving G37-tRNA. In this mechanism, D169 is the general base to abstract the N1 proton from G37, while the deprotonation is accompanied by developing electron density on the O6 of G37. The developing negative charge on O6 of G37 is stabilized through coordination with Mg2+ and by hydrogen-bond interaction with the side chain of R154. The charge stabilization of O6 in turn facilitates Mg2+ to coordinate with the general base D169 and to help it to align more properly for proton abstraction. The activated N1 nucleophile is then poised for nucleophilic attack on the sulfonium center of AdoMet, resulting in synthesis of m1G37-tRNA and release of AdoHcy. The rate-limiting step is assigned to the action of D169, rather than to the protonation of the leaving group, due to the importance of D169 and the increase of activity as the proton concentration is lowered Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 additional information the m1G37 methylation by TrmD does not need any other prior modification, aminoacylation, or even CCA addition to tRNA. Transient nature of Mg2+ is consistent with the proposed catalytic mechanism involving G37-tRNA. In this mechanism, D169 is the general base to abstract the N1 proton from G37, while the deprotonation is accompanied by developing electron density on the O6 of G37. The developing negative charge on O6 of G37 is stabilized through coordination with Mg2+ and by hydrogen-bond interaction with the side chain of R154. The charge stabilization of O6 in turn facilitates Mg2+ to coordinate with the general base D169 and to help it to align more properly for proton abstraction. The activated N1 nucleophile is then poised for nucleophilic attack on the sulfonium center of AdoMet, resulting in synthesis of m1G37-tRNA and release of AdoHcy. The rate-limiting step is assigned to the action of D169, rather than to the protonation of the leaving group, due to the importance of D169 and the increase of activity as the proton concentration is lowered Haemophilus influenzae
2.1.1.228 physiological function while the greatest majority of the tRNA modifying enzymes are nonessential for life, acting for example as a chaperone to modulate tRNA activity, a very small number of these enzymes are absolutely required for cell growth and survival. TrmD is an example of one of these essential enzymes, responsible for methyl transfer from AdoMet to the N1 position of the G37 base to synthesize m1G37 on tRNA. The methylated m1G37 is on the 3?-side of the anticodon, and it is necessary for suppressing tRNA frameshifting during protein synthesis on the ribosome TrmD is an S-adenosyl methionine (AdoMet)-dependent methyl transferase that synthesizes the methylated m1G37 in tRNA. TrmD is specific to and essential for bacterial growth, and it is fundamentally distinct from its eukaryotic and archaeal counterpart Trm5. TrmD is unusual by using a topological protein knot to bind AdoMet. Despite its restricted mobility, the TrmD knot has complex dynamics necessary to transmit the signal of AdoMet binding to promote tRNA binding and methyl transfer. TrmD is unique among AdoMet-dependent methyl transferases in that it requires Mg2+ in the catalytic mechanism. The Mg2+ dependence is important for regulating Mg2+ transport to Salmonella for survival of the pathogen in the host cell. The trefoil knot of TrmD is required for the catalytic mechanism in three ways. Synthesis of m1G37-tRNA by TrmD is a posttranscriptional event Salmonella enterica subsp. enterica serovar Typhimurium
2.1.1.228 physiological function while the greatest majority of the tRNA modifying enzymes are nonessential for life, acting for example as a chaperone to modulate tRNA activity, a very small number of these enzymes are absolutely required for cell growth and survival. TrmD is an example of one of these essential enzymes, responsible for methyl transfer from AdoMet to the N1 position of the G37 base to synthesize m1G37 on tRNA. TrmD is an S-adenosyl methionine (AdoMet)-dependent methyl transferase that synthesizes the methylated m1G37 in tRNA. TrmD is specific to and essential for bacterial growth, and it is fundamentally distinct from its eukaryotic and archaeal counterpart Trm5. TrmD is unusual by using a topological protein knot to bind AdoMet. Despite its restricted mobility, the TrmD knot has complex dynamics necessary to transmit the signal of AdoMet binding to promote tRNA binding and methyl transfer. TrmD is unique among AdoMet-dependent methyl transferases in that it requires Mg2+ in the catalytic mechanism Aquifex aeolicus
2.1.1.228 physiological function while the greatest majority of the tRNA modifying enzymes are nonessential for life, acting for example as a chaperone to modulate tRNA activity, a very small number of these enzymes are absolutely required for cell growth and survival. TrmD is an example of one of these essential enzymes, responsible for methyl transfer from AdoMet to the N1 position of the G37 base to synthesize m1G37 on tRNA. TrmD is an S-adenosyl methionine (AdoMet)-dependent methyl transferase that synthesizes the methylated m1G37 in tRNA. TrmD is specific to and essential for bacterial growth, and it is fundamentally distinct from its eukaryotic and archaeal counterpart Trm5. TrmD is unusual by using a topological protein knot to bind AdoMet. Despite its restricted mobility, the TrmD knot has complex dynamics necessary to transmit the signal of AdoMet binding to promote tRNA binding and methyl transfer. TrmD is unique among AdoMet-dependent methyl transferases in that it requires Mg2+ in the catalytic mechanism. The trefoil knot of TrmD is required for the catalytic mechanism in three ways. Synthesis of m1G37-tRNA by TrmD is a posttranscriptional event Escherichia coli
2.1.1.228 physiological function while the greatest majority of the tRNA modifying enzymes are nonessential for life, acting for example as a chaperone to modulate tRNA activity, a very small number of these enzymes are absolutely required for cell growth and survival. TrmD is an example of one of these essential enzymes, responsible for methyl transfer from AdoMet to the N1 position of the G37 base to synthesize m1G37 on tRNA. TrmD is an S-adenosyl methionine (AdoMet)-dependent methyl transferase that synthesizes the methylated m1G37 in tRNA. TrmD is specific to and essential for bacterial growth, and it is fundamentally distinct from its eukaryotic and archaeal counterpart Trm5. TrmD is unusual by using a topological protein knot to bind AdoMet. Despite its restricted mobility, the TrmD knot has complex dynamics necessary to transmit the signal of AdoMet binding to promote tRNA binding and methyl transfer. TrmD is unique among AdoMet-dependent methyl transferases in that it requires Mg2+ in the catalytic mechanism. The trefoil knot of TrmD is required for the catalytic mechanism in three ways. Synthesis of m1G37-tRNA by TrmD is a posttranscriptional event Haemophilus influenzae