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Information on EC 2.1.1.228 - tRNA (guanine37-N1)-methyltransferase and Organism(s) Aquifex aeolicus and UniProt Accession O67463
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2.1.1.228 tRNA (guanine37-N1)-methyltransferaseIUBMB Comments
This enzyme is important for the maintenance of the correct reading frame during translation. Unlike TrmD from Escherichia coli, which recognizes the G36pG37 motif preferentially, the human enzyme (encoded by TRMT5) also methylates inosine at position 37 .
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Word Map
- 2.1.1.228
- methyltransferases
-
anticodon
- adomet
- 1-methylguanosine
- drug development
-
n2-guanine
- trmt10a
- 1-methyladenine
-
adomet-dependent
- 5-methyluridine
- trmfo
-
n1-methylation
-
methyl-deficient
- 7-methylguanine
-
spout
-
epitranscriptome
-
nsun2-mediated
- medicine
The taxonomic range for the selected organisms is: Aquifex aeolicus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
+
guanine37 in tRNA
=
+
N1-methylguanine37 in tRNA
Synonyms
trna methyltransferase, trna(m1g37)methyltransferase, patrmd, patrm5a, trna(m(1)g37)methyltransferase, trm5p, attrm5a, trna (m1g37) methyltransferase, trmt5, trna (guanosine-1) methyltransferase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PATHWAY SOURCE
PATHWAYS
-
-, -, -
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:tRNA (guanine37-N1)-methyltransferase
This enzyme is important for the maintenance of the correct reading frame during translation. Unlike TrmD from Escherichia coli, which recognizes the G36pG37 motif preferentially, the human enzyme (encoded by TRMT5) also methylates inosine at position 37 [4].
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + guanine37 in tRNA
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Aquifex aeolicus tRNAArg(ACG)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Aquifex aeolicus tRNAArg(ACG)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Aquifex aeolicus tRNAArg(CCG)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Aquifex aeolicus tRNAArg(CCG)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Aquifex aeolicus tRNAGln(UUG)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Aquifex aeolicus tRNAGln(UUG)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Aquifex aeolicus tRNAHis(GUG)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Aquifex aeolicus tRNAHis(GUG)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Aquifex aeolicus tRNALeu(CAG)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Aquifex aeolicus tRNALeu(CAG)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Aquifex aeolicus tRNAPro(GGG)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Aquifex aeolicus tRNAPro(GGG)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Haloferax volcanii tRNACys(GCA)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Haloferax volcanii tRNACys(GCA)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Haloferax volcanii tRNALeu(CAA)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Haloferax volcanii tRNALeu(CAA)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Haloferax volcanii tRNATrp(CCA)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Haloferax volcanii tRNATrp(CCA)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in Haloferax volcanii tRNATyr(GUA)
S-adenosyl-L-homocysteine + N1-methylguanine37 in Haloferax volcanii tRNATyr(GUA)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in in Escherichia coli tRNALeu(CAG)
S-adenosyl-L-homocysteine + N1-methylguanine37 in in Escherichia coli tRNALeu(CAG)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in tRNA
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
S-adenosyl-L-methionine + guanine37 in yeast tRNAPhe(GAA)
S-adenosyl-L-homocysteine + N1-methylguanine37 in yeast tRNAPhe(GAA)
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in tRNA
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
-
-
-
?
S-adenosyl-L-methionine + guanine37 in tRNA
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
the enzyme methylates tRNA transcripts possessing an A36G37 sequence as well as tRNA transcripts possessing a G36G37 sequence. tRNA transcripts possessing pyrimidine36G37 are not methylated at all. The modified nucleoside and the position in yeast tRNA(Phe) transcript are confirmed by LC/MS. Nine truncated tRNA molecules are tested to clarify the additional recognition site. The TrmD protein efficiently methylates the micro helix corresponding to the anti-codon arm. Because the disruption of the anti-codon stem causes the complete loss of the methyl group acceptance activity, the anti-codon stem is essential for the recognition. The existence of the D-arm structure inhibits the activity
-
-
?
additional information
?
-
TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon
-
-
-
additional information
?
-
TrmD can methylate a truncated tRNA, in which T- and D-arms have been deleted, the anticodon-arm region is mainly protected. The tRNA recognition mechanism of Aquifex aeolicus TrmD shows that a micro-helix RNA corresponding to the anticodon-arm is the minimal substrate for this enzyme
-
-
-
additional information
?
-
-
no activity with guanine37 in yeast tRNAAsp(GUC) possessing a C36G37 sequence, guanine37 in Haloferax volcanii tRNAGlu(UUC) possessing a C36G37 sequence, guanine37 in yeast tRNAPhe A36U mutant(GAU) possessing a U36G37 sequence, guanine37 in Escherichia coli tRNASer(UGA) possessing a A36G37 sequence
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + guanine37 in tRNA
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
-
-
?
S-adenosyl-L-methionine + guanine37 in tRNA
S-adenosyl-L-homocysteine + N1-methylguanine37 in tRNA
-
-
-
-
?
additional information
?
-
TrmD synthesizes the methylated m1G37 on bacterial tRNAs that contain both G37 and a preceding G36, the 3'-nucleotide of the anticodon
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
methyl transfer by TrmD requires Mg2+ in the catalytic mechanism, kinetics
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
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
KM-values for truncated tRNAPhe variants
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
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
physiological function
additional information
evolution
the enzyme TrmD belongs to the 2'-O-methyltransferase family, previously SpoU family of enzymes, conserved motifs in the TrmH (SpoU) and TrmD families, overview. Comparisons of topological knot structures in TrmH (SpoU) and TrmD. AdoMet-dependent enzymes can be divided into more than five classes according to the structure of their catalytic domain. Most methyltransferases have a Rossman fold catalytic domain and are classified as class I enzymes. In contrast, members of SPOUT RNA methyltransferase superfamily are classified as class IV enzymes, whose catalytic domain forms a deep trefoil (topological) knot. TrmD from Aquifex aeolicus belongs to the m1G37 methyltransferases
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
physiological function
this protein is important for the maintenance of the correct reading frame during translation
physiological function
enzyme TrmD catalyzes the transfer of methyl group from AdoMet to N1-atom of G37 in tRNA to form m1G37
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
additional information
Aquifex aeolicus TrmD can methylate G37 in the A36G37 sequence, showing that purine36 is a positive determinant for the TrmD. Formation of a disulfide bond between the two subunits stabilizes the dimer structure of Aquifex aeolicus TrmD and is required for enzymatic activity at high temperatures
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
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
additional information
dimer
TrmD is an obligated homodimer that places each active site at the dimer interface
additional information
knot structures, domain arrangements, subunit structures and reaction mechanisms of tRNA methyltransferases with a SPOUT fold, overview
additional information
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
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C20S
the C20S mutant protein forms a dimer structure even though it is missing the Cys20Cys20 disulfide bond between its two subunits. Incubation at 85°C for 20 min causes the precipitation of more than half of the C20S protein, while more than 70% of the wild-type enzyme is soluble at that temperature. Methyl-transfer activity of the C20S mutant protein is slightly less than that of the wild-type enzyme at 70°C. Comparison of the CD-spectra of wild-type and C20S proteins reveals that some of the alpha-helices in the C20S mutant protein are less tightly packed than the alpha-helices of the wild-type enzyme at 70°C
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
the Cys20Cys20 disulfide bond between its two subunits enhances the protein stability at 85°C
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
TrmD is ranked as a high-priority antimicrobial target
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Takeda, H.; Toyooka, T.; Ikeuchi, Y.; Yokobori, S.; Okadome, K.; Takano, F.; Oshima, T.; Suzuki, T.; Endo, Y.; Hori, H.
The substrate specificity of tRNA (m1G37) methyltransferase (TrmD) from Aquifex aeolicus
Genes Cells
11
1353-1365
2006
Aquifex aeolicus
Toyooka, T.; Awai, T.; Kanai, T.; Imanaka, T.; Hori, H.
Stabilization of tRNA (mG37) methyltransferase [TrmD] from Aquifex aeolicus by an intersubunit disulfide bond formation
Genes Cells
13
807-816
2008
Aquifex aeolicus (O67463)
Liu, J.; Wang, W.; Shin, D.H.; Yokota, H.; Kim, R., Kim, S.H.
Crystal structure of tRNA (m1G37) methyltransferase from Aquifex aeolicus at 2.6 A resolution: a novel methyltransferase fold
Proteins
53
326-328
2003
Aquifex aeolicus (O67463), Aquifex aeolicus
Hori, H.
Transfer RNA methyltransferases with a SpoU-TrmD (SPOUT) fold and their modified nucleosides in tRNA
Biomolecules
7
E23
2017
Haemophilus influenzae (A0A0D0GZF5), Aquifex aeolicus (O67463), Escherichia coli (P0A873)
Hou, Y.; Matsubara, R.; Takase, R.; Masuda, I.; Sulkowska, J.
TrmD A methyl transferase for tRNA methylation with m1G37
Enzymes
41
89-115
2017
Haemophilus influenzae (A0A0D0GZF5), Aquifex aeolicus (O67463), Escherichia coli (P0A873), Salmonella enterica subsp. enterica serovar Typhimurium (P36245), Salmonella enterica subsp. enterica serovar Typhimurium SGSC1412 (P36245), Salmonella enterica subsp. enterica serovar Typhimurium ATCC 700720 (P36245)
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