Literature summary for 2.1.1.220 extracted from

Finer-Moore, J.; Czudnochowski, N.; OConnell, J.I.; Wang, A.; Stroud, R.
Crystal structure of the human tRNA m1A58 methyltransferase-tRNA3 Lys complex: Refolding of Substrate tRNA Allows Access to the Methylation Target (2015), J. Mol. Biol., 427, 3862-3876.

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Application

Application	Comment	Organism
drug development	the enzyme crystal structures serve as templates for design of inhibitors that can be used to test tRNA m1A58 MTase's impact on retroviral priming and transcription	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of C-terminally His-tagged enzyme in Escherichia coli strain BL21(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
human enzyme tRNA m1A58 MTase in complex with human tRNA3Lys and cofactors S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, hanging drop vapor diffusion method, mixing of 0.001 ml of 4.8 mg/ml protein in 50 mM HEPES, pH 7.5, 0.0664 mM tRNA3Lys, 2 mM S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, and 1 mM MgCl2, with 0.001 ml of reservoir solution containing 0.1 M Na acetate, pH 4.8-5.0, 2% w/v PEG 4000 and 15% v/v methyl-2,4-pentanediol, 16°C, 4-7 days, X-ray diffraction structure determination and analysis at 2.2-4.0 A resolution, molecular replacement	Homo sapiens

Crystallization (Comment)

Organism

human enzyme tRNA m1A58 MTase in complex with human tRNA3Lys and cofactors S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, hanging drop vapor diffusion method, mixing of 0.001 ml of 4.8 mg/ml protein in 50 mM HEPES, pH 7.5, 0.0664 mM tRNA3Lys, 2 mM S-adenosyl-L-methionine or S-adenosyl-L-homocysteine, and 1 mM MgCl2, with 0.001 ml of reservoir solution containing 0.1 M Na acetate, pH 4.8-5.0, 2% w/v PEG 4000 and 15% v/v methyl-2,4-pentanediol, 16°C, 4-7 days, X-ray diffraction structure determination and analysis at 2.2-4.0 A resolution, molecular replacement

Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
S-adenosyl-L-methionine + adenine58 in tRNA	Homo sapiens	-	S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA	-	?
S-adenosyl-L-methionine + adenine58 in tRNA3Lys	Homo sapiens	-	S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA3Lys	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q96FX7	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant C-terminally His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, cleavage of the tag by 3C protease, and gel filtration	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
S-adenosyl-L-methionine + adenine58 in tRNA	-	Homo sapiens	S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA	-	?
S-adenosyl-L-methionine + adenine58 in tRNA3Lys	-	Homo sapiens	S-adenosyl-L-homocysteine + N1-methyladenine58 in tRNA3Lys	-	?

Subunits

Subunits	Comment	Organism
More	Trm6 is less conserved with respect to TrmI than Trm61 and lacks a cofactor-binding pocket, enzyme quaternary structure, overview	Homo sapiens
tetramer	dimer of heterodimers in which each heterodimer comprises a catalytic chain, Trm61, and a homologous but noncatalytic chain, Trm6, repurposed as a tRNA-binding subunit that acts in trans, crystal structure analysis	Homo sapiens

Synonyms

Synonyms	Comment	Organism
m1A58MTase	-	Homo sapiens
tRNA m1A58 methyltransferase	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
S-adenosyl-L-methionine	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	m1A58 MTase is composed of two subunits, a catalytic component, Trm61, and an RNA-binding component, Trm6. tRNAs bind across the dimer interface such that Trm6 from the opposing heterodimer brings A58 into the active site of Trm61. T-loop and D-loop are splayed apart showing how A58, normally buried in tRNA, becomes accessible for modification, mechanisms of modifying internal sites in folded tRNA, overview. 2Fold related tRNAs bind across the tetramer interface, active site structure analysis. m1A58 MTase uses induced fit to access its target base	Homo sapiens
physiological function	m1A58 modification of tRNA3Lys also has a role in replication of HIV in humans, human tRNA3 Lys is the primer for reverse transcription of HIV, the 3' end is complementary to the primer-binding site on HIV RNA. The complementarity ends at the 18th base, A58, which in tRNA3 Lys is modified to remove Watson-Crick pairing. tRNA m1A58 methyltransferase methylates N1 of A58, which is buried in the TPsiC-loop of tRNA, from cofactor S-adenosyl-L-methionine. This conserved tRNA modification is essential for stability of initiator tRNA	Homo sapiens