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IUBMB CommentsThe enzyme from non-segmented negative strain (NNS) viruses (e.g. rhabdoviruses) catalyses two successive methylations. In higher eukaryotes the two methylations occur in the reverse order and are catalysed by two different enzymes (cf. EC 2.1.1.56, mRNA (guanine-N7)-methyltransferase, and EC 2.1.1.57, methyltransferase cap1) that do not required a specific motif.
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2 S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
2 S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
S-adenosyl-L-homocysteine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-methionine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
2 S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
2 S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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2 S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
2 S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
S-adenosyl-L-homocysteine + G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
S-adenosyl-L-homocysteine + G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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2 S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
2 S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
S-adenosyl-L-homocysteine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-methionine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
2 S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
2 S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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2 S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
2 S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
S-adenosyl-L-homocysteine + G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAACA-[mRNA]
S-adenosyl-L-homocysteine + G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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S-adenosyl-L-methionine + G(5')pppAmACA-[mRNA]
S-adenosyl-L-homocysteine + m7G(5')pppAmACA-[mRNA]
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metabolism
vesicular stomatitis virus L protein typically modifies the 2'-Oposition of the cap prior to the G-N-7 position and G-N-7 methylation is diminished by pre-2'-O methylation of the substrate RNA. Amino acid substitutions in the C terminus of L that prevent all cap methylation in recombinant VSV partially retain the ability to G-N-7 methylate a pre-2'-O-methylated RNA, therefore uncoupling the effect of substitutions in the C terminus of the L protein on the two methylations. The 2'-O and G-N-7 methylase activities act specifically on RNA substrates that contain the conserved elements of a vesicular stomatitis virus mRNA start at the 5'-terminus
metabolism
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vesicular stomatitis virus L protein typically modifies the 2'-Oposition of the cap prior to the G-N-7 position and G-N-7 methylation is diminished by pre-2'-O methylation of the substrate RNA. Amino acid substitutions in the C terminus of L that prevent all cap methylation in recombinant VSV partially retain the ability to G-N-7 methylate a pre-2'-O-methylated RNA, therefore uncoupling the effect of substitutions in the C terminus of the L protein on the two methylations. The 2'-O and G-N-7 methylase activities act specifically on RNA substrates that contain the conserved elements of a vesicular stomatitis virus mRNA start at the 5'-terminus
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physiological function
enzyme functions for both 2'-O and G-N-7 methylations during RNA cap formation. VSV L typically modifies the 2'-O position of the cap prior to the G-N-7 position and G-N-7 methylation is diminished by pre-2'-O methylation of the substrate RNA. Amino acid substitutions in the C terminus of L that prevent all cap methylation in recombinant vesicular stomatitis virus partially retain the ability to G-N-7 methylate a pre-2'-O-methylated RNA, uncoupling the effect of substitutions in the C terminus of the L protein on the two methylations. The 2'-O and G-N-7 methylase activities act specifically on RNA substrates that contain the conserved elements of a vesicular stomatitis virus mRNA start at the 5' terminus
physiological function
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enzyme functions for both 2'-O and G-N-7 methylations during RNA cap formation. VSV L typically modifies the 2'-O position of the cap prior to the G-N-7 position and G-N-7 methylation is diminished by pre-2'-O methylation of the substrate RNA. Amino acid substitutions in the C terminus of L that prevent all cap methylation in recombinant vesicular stomatitis virus partially retain the ability to G-N-7 methylate a pre-2'-O-methylated RNA, uncoupling the effect of substitutions in the C terminus of the L protein on the two methylations. The 2'-O and G-N-7 methylase activities act specifically on RNA substrates that contain the conserved elements of a vesicular stomatitis virus mRNA start at the 5' terminus
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structure of rabies virus L protein bound with its phosphoprotein cofactor, at 3.3 A resolution. In the methyltransferase domain, a shared GxGxG motif forms the binding site for the methyl donor, S-adenosylmethionine, and a conserved set of charged residues Lys1685, Asp1797, Lys1829, and Glu1867 forms the catalytic tetrad
Lyssavirus rabies
domain VI of the VSV L protein contains a 2'-O-ribose methyltransferase (MTase) domain. Structural homology model of residues 1644-1842 within domain VI. The binding pocket consists of seven beta-strands and six alpha-helices. Highly conserved glycines are lining the interior of the pocket. Conserved aspartic acid D1762 is positioned at the perimeter of the pocket and interacts with invariantly conserved residues K1651, K1795, and E1833 to constitute the catalytic tetrad
the multifunctional large polymerase protein L is organized L into a ring domain containing the RNA polymerase and an appendage of three globular domains containing the cap-forming activities. The capping enzyme maps to a globular domain, which is juxtaposed to the ring, and the cap methyltransferase maps to a more distal and flexibly connected globule. Upon viral phosphoprotein binding, L undergoes a significant rearrangement
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D1762E
mutant is able to form plaques at 31°C in Vero cells with significantly reduced titers at 24 hr compared to wild-type
D1762G
mutant is able to form plaques at 31°C in Vero cells with significantly reduced titers at 24 hr compared to wild-type
D1762N
mutant is able to form plaques at 31°C in Vero cells with significantly reduced titers at 24 hr compared to wild-type
G1670A
mice inoculated with G1670A, which is defective only in G-N-7 methylation, are attenuated in vivo yet retain a low level of virulence
G1672P
mutant is able to form plaques at 31°C in Vero cells
G1674P
mutant is able to form plaques at 31°C in Vero cells, but not at 39°C
G1675P
mutant is able to form plaques at 31°C in Vero cells, but not at 39°C
G4A
mutant virus is completely defective in both G-N-7 and 2'-O methylation, exhibits low virulence in mice despite productive viral replication is not detected in lung and brain
L1716T
mutant is able to form plaques at 31°C in Vero cells and displays a pronounced growth restriction at 39°C
L1716Y
mutant is able to form plaques at 31°C in Vero cells, but not at 39°C
G4A
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mutant virus is completely defective in both G-N-7 and 2'-O methylation, exhibits low virulence in mice despite productive viral replication is not detected in lung and brain
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D1762A
defective in both G-N-7 and 2'-O methylation, and highly attenuated in mice. Mutant virus elicits a high level of neutralizing antibody and provides full protection against challenge with the virulent VSV
D1762A
mutation inhibits both 2'-O and G-N-7 methylations
D1762A
mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
E1833Q
defective in both G-N-7 and 2'-O methylation, and highly attenuated in mice. Mutant virus elicits a high level of neutralizing antibody and provides full protection against challenge with the virulent VSV
E1833Q
mutation inhibits both 2'-O and G-N-7 methylations
E1833Q
mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
G1672A
mice inoculated with G1672A, which is defective only in G-N-7 methylation, are attenuated in vivo yet retain a low level of virulence
G1672A
mutant is able to form plaques at 31°C in Vero cells
K1651A
defective in both G-N-7 and 2'-O methylation, and highly attenuated in mice. Mutant virus elicits a high level of neutralizing antibody and provides full protection against challenge with the virulent VSV
K1651A
mutation inhibits both 2'-O and G-N-7 methylations
K1651A
mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
K1795A
mutation inhibits both 2'-O and G-N-7 methylations
K1795A
mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
D1762A
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mutation inhibits both 2'-O and G-N-7 methylations
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D1762A
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defective in both G-N-7 and 2'-O methylation, and highly attenuated in mice. Mutant virus elicits a high level of neutralizing antibody and provides full protection against challenge with the virulent VSV
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D1762A
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mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
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E1833Q
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mutation inhibits both 2'-O and G-N-7 methylations
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E1833Q
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defective in both G-N-7 and 2'-O methylation, and highly attenuated in mice. Mutant virus elicits a high level of neutralizing antibody and provides full protection against challenge with the virulent VSV
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E1833Q
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mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
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G1672A
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mice inoculated with G1672A, which is defective only in G-N-7 methylation, are attenuated in vivo yet retain a low level of virulence
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G1672A
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mutant is able to form plaques at 31°C in Vero cells
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K1651A
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mutation inhibits both 2'-O and G-N-7 methylations
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K1651A
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defective in both G-N-7 and 2'-O methylation, and highly attenuated in mice. Mutant virus elicits a high level of neutralizing antibody and provides full protection against challenge with the virulent VSV
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K1651A
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mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
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K1795A
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mutation inhibits both 2'-O and G-N-7 methylations
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K1795A
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mutation inhibits both 2'-O and G-N-7 methylations. When the RNA substrate is premethylated at the 2'-O position, G-N-7 methylation is restored to between 7 and 16%, compared with 50% for wild-type L
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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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Rahmeh, A.; Jianrong, L.; Kranzusch, P.; Whelan, S.
Ribose 2'-O methylation of the vesicular stomatitis virus mRNA cap precedes and facilitates subsequent guanine-N-7 methylation by the large polymerase protein
J. Virol.
83
11043-11050
2009
vesicular stomatitis Indiana virus (P03523), vesicular stomatitis Indiana virus San Juan (P03523)
brenda
Ma, Y.; Wei, Y.; Zhang, X.; Zhang, Y.; Cai, H.; Zhu, Y.; Shilo, K.; Oglesbee, M.; Krakowka, S.; Whelan, S.P.; Li, J.
mRNA cap methylation influences pathogenesis of vesicular stomatitis virus in vivo
J. Virol.
88
2913-2926
2014
vesicular stomatitis Indiana virus (P03523), vesicular stomatitis Indiana virus San Juan (P03523)
brenda
Rahmeh, A.A.; Schenk, A.D.; Danek, E.I.; Kranzusch, P.J.; Liang, B.; Walz, T.; Whelan, S.P.
Molecular architecture of the vesicular stomatitis virus RNA polymerase
Proc. Natl. Acad. Sci. USA
107
20075-20080
2010
vesicular stomatitis Indiana virus (P03523), vesicular stomatitis Indiana virus San Juan (P03523)
brenda
Horwitz, J.; Jenni, S.; Harrison, S.; Whelan, S.
Structure of a rabies virus polymerase complex from electron cryo-microscopy
Proc. Natl. Acad. Sci. USA
117
2099-2107
2020
Lyssavirus rabies (P16289), Lyssavirus rabies SAD B19 (P16289)
brenda
Galloway, S.E.; Richardson, P.E.; Wertz, G.W.
Analysis of a structural homology model of the 2-O-ribose methyltransferase domain within the vesicular stomatitis virus L protein
Virology
382
69-82
2008
vesicular stomatitis Indiana virus (P03523), vesicular stomatitis Indiana virus San Juan (P03523)
brenda