Literature summary for 2.1.1.348 extracted from

Wang, P.; Doxtader, K.A.; Nam, Y.
Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases (2016), Mol. Cell, 63, 306-317 .

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Cloned(Commentary)

Cloned (Comment)	Organism
expression in Escherichia coli	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. The heterodimeric complex of methyltransferase domains, combined with CCCH motifs constitute the minimally required regions for creating m6A modifications in vitro. Mettl3 is the catalytically active subunit while Mettl14 plays a structural role critical for substrate recognition	Homo sapiens

Crystallization (Comment)

Organism

crystal structures of the complex of Mettl3/Mettl14 methyltransferase domains in apo form as well as with bound S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) in the catalytic site. The heterodimeric complex of methyltransferase domains, combined with CCCH motifs constitute the minimally required regions for creating m6A modifications in vitro. Mettl3 is the catalytically active subunit while Mettl14 plays a structural role critical for substrate recognition

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
D395A	change of the DPPW catalytic motif to APPW in METTL3, abrogates the ability of its complex with wild type METTL14 to methylate RNA	Homo sapiens
E192A	change of EPPL to APPL in METTL14, little effect on methylation capacity if wild type METTL3 is present	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
S-adenosyl-L-methionine + adenine in mRNA	Homo sapiens	-	S-adenosyl-L-homocysteine + N6-methyladenine in mRNA	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q86U44 and Q9HCE5	Q86U44 i.e. catalytic subunit METTL3, Q9HCE5 i.e non-catalytic subunit METTL14	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	consensus sequence for methylation of RNA is GGACU. The single transition mutation, GGACU to GGAUU, is sufficient to significantly reduce methylation levels	Homo sapiens	?	-	?
S-adenosyl-L-methionine + adenine in 5'-UACACUCGAUCU-GGACU-AAAGCUGCUC	-	Homo sapiens	homocysteine + 5'-UACACUCGAUCU-GG-(N6-methyl)ACU-AAAGCUGCUC	-	?
S-adenosyl-L-methionine + adenine in mRNA	-	Homo sapiens	S-adenosyl-L-homocysteine + N6-methyladenine in mRNA	-	?