Literature summary for 2.1.1.228 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 .

Search for more literature for 2.1.1.228

Application

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

Cloned(Commentary)

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

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	can substitute Mg2+ to lesser extent	Aquifex aeolicus
Ca2+	can substitute Mg2+ to lesser extent	Escherichia coli
Ca2+	can substitute Mg2+ to lesser extent	Salmonella enterica subsp. enterica serovar Typhimurium
Ca2+	can substitute Mg2+ to lesser extent	Haemophilus influenzae
Mg2+	methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics	Aquifex aeolicus
Mg2+	methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics	Escherichia coli
Mg2+	methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics	Salmonella enterica subsp. enterica serovar Typhimurium
Mg2+	methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics	Haemophilus influenzae
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
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
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
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
Ni2+	can substitute Mg2+ to lesser extent	Aquifex aeolicus
Ni2+	can substitute Mg2+ to lesser extent	Escherichia coli
Ni2+	can substitute Mg2+ to lesser extent	Salmonella enterica subsp. enterica serovar Typhimurium
Ni2+	can substitute Mg2+ to lesser extent	Haemophilus influenzae

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
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	?	-	-
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	?	-	-
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	?	-	-
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	?	-	-
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	?	-	-
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	?	-	-
S-adenosyl-L-methionine + guanine37 in tRNA	Aquifex aeolicus	-	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	Escherichia coli	-	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	Salmonella enterica subsp. enterica serovar Typhimurium	-	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	Haemophilus influenzae	-	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412	-	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720	-	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?

Organism

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

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
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	?	-	-
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	?	-	-
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	?	-	-
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	?	-	-
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	?	-	-
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	?	-	-
S-adenosyl-L-methionine + guanine37 in tRNA	-	Aquifex aeolicus	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	-	Escherichia coli	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	-	Salmonella enterica subsp. enterica serovar Typhimurium	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	-	Haemophilus influenzae	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	-	Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?
S-adenosyl-L-methionine + guanine37 in tRNA	-	Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720	S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA	-	?

Subunits

Subunits	Comment	Organism
dimer	TrmD is an obligated homodimer that places each active site at the dimer interface	Aquifex aeolicus
dimer	TrmD is an obligated homodimer that places each active site at the dimer interface	Escherichia coli
dimer	TrmD is an obligated homodimer that places each active site at the dimer interface	Salmonella enterica subsp. enterica serovar Typhimurium
dimer	TrmD is an obligated homodimer that places each active site at the dimer interface	Haemophilus influenzae
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
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
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
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

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

Cofactor

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

General Information

General Information	Comment	Organism
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

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Release 2023.1 (January 2023)