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Literature summary for 2.7.7.88 extracted from

  • Ogino, T.; Green, T.J.
    Transcriptional control and mRNA capping by the GDP polyribonucleotidyltransferase domain of the rabies virus large protein (2019), Viruses, 11, 504 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development the large (L) protein of the rabies virus (RABV) is a multifunctional RNA-dependent RNA-polymerase, which is one of the most attractive targets for developing antiviral agents Lyssavirus rabies

Cloned(Commentary)

Cloned (Comment) Organism
gene L, genomic structure, transcription and replication of the rabies virus (RABV) genome. The negative-strand RABV genome wrapped with the nucleocapsid (N) proteins serves as a template for transcription and replication. The RNA-dependent RNA polymerase (RdRp, the complex between large (L) and (P) phosphoproteins) sequentially transcribes the leader region (Le) and five internal genes (N, P, M, G, and L) in the genome into the leader RNA (LeRNA) and five monocistronic mRNAs with the 5'-cap 1 and 3'-poly(A) structures by the stop-start transcription mechanism Lyssavirus rabies

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Lyssavirus rabies

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
(5')pppAACA-[mRNA] + GDP Lyssavirus rabies overall reaction diphosphate + G(5')pppAACA-[mRNA]
-
?
(5')pppAACA-[mRNA] + GDP Lyssavirus rabies PV overall reaction diphosphate + G(5')pppAACA-[mRNA]
-
?
(5')pppAACA-[mRNA] + GDP Lyssavirus rabies Pasteur vaccins overall reaction diphosphate + G(5')pppAACA-[mRNA]
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?
a 5'-end triphospho-adenylyl-adenylyl-cytidyl-adenosine in mRNA + GDP + H+ Lyssavirus rabies overall reaction a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidyl-adenosine in mRNA + diphosphate
-
?
a 5'-end triphospho-adenylyl-adenylyl-cytidyl-adenosine in mRNA + GDP + H+ Lyssavirus rabies PV overall reaction a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidyl-adenosine in mRNA + diphosphate
-
?
a 5'-end triphospho-adenylyl-adenylyl-cytidyl-adenosine in mRNA + GDP + H+ Lyssavirus rabies Pasteur vaccins overall reaction a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidyl-adenosine in mRNA + diphosphate
-
?

Organism

Organism UniProt Comment Textmining
Lyssavirus rabies P11213 RABV
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Lyssavirus rabies Pasteur vaccins P11213 RABV
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Lyssavirus rabies PV P11213 RABV
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(5')pppAACA-[mRNA] + GDP overall reaction Lyssavirus rabies diphosphate + G(5')pppAACA-[mRNA]
-
?
(5')pppAACA-[mRNA] + GDP overall reaction Lyssavirus rabies PV diphosphate + G(5')pppAACA-[mRNA]
-
?
(5')pppAACA-[mRNA] + GDP overall reaction Lyssavirus rabies Pasteur vaccins diphosphate + G(5')pppAACA-[mRNA]
-
?
a 5'-end triphospho-adenylyl-adenylyl-cytidyl-adenosine in mRNA + GDP + H+ overall reaction Lyssavirus rabies a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidyl-adenosine in mRNA + diphosphate
-
?
a 5'-end triphospho-adenylyl-adenylyl-cytidyl-adenosine in mRNA + GDP + H+ overall reaction Lyssavirus rabies PV a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidyl-adenosine in mRNA + diphosphate
-
?
a 5'-end triphospho-adenylyl-adenylyl-cytidyl-adenosine in mRNA + GDP + H+ overall reaction Lyssavirus rabies Pasteur vaccins a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidyl-adenosine in mRNA + diphosphate
-
?
additional information structure-function analysis, and substrate binding structure analysis, overview Lyssavirus rabies ?
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-
additional information structure-function analysis, and substrate binding structure analysis, overview Lyssavirus rabies PV ?
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-
additional information structure-function analysis, and substrate binding structure analysis, overview Lyssavirus rabies Pasteur vaccins ?
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-

Subunits

Subunits Comment Organism
More the RABV L protein is predicted to have an N-terminal (NTD, composed of subdomains I and II), RdRp, bridge, mRNA capping enzyme (GDP polyribonucleotidyltransferase, PRNTase), connector (CD), methyltransferase (MTase), and C-terminal (CTD) domains, model of the rabies virus (RABV) large (L) protein, and domain organization, three-dimensional structure of the RABV L protein, overview. The putative RABV PRNTase domain (residues 1093-1349) shares five conserved motifs, Rx(3)Wx(3-8)PhixGxdeltax(P/A) (motif A), (Y/W)PhiGSxT (motif B), W (motif C), HR (motif D), and deltaxxPhix(F/Y)QxxPhi (motif E) (Phi = hydrophobic, delta = hydrophilic amino acids). Structure analysis, overview Lyssavirus rabies

Synonyms

Synonyms Comment Organism
More cf. EC 2.7.7.48 Lyssavirus rabies
mRNA capping enzyme
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Lyssavirus rabies
PRNTase
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Lyssavirus rabies
rabies virus large protein
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Lyssavirus rabies

General Information

General Information Comment Organism
evolution the putative RABV PRNTase domain (residues 1093-1349) shares five conserved motifs, Rx(3)Wx(3-8)PhixGxdeltax(P/A) (motif A), (Y/W)PhiGSxT (motif B), W (motif C), HR (motif D), and deltaxxPhix(F/Y)QxxPhi (motif E) (Phi = hydrophobic, delta = hydrophilic amino acids) with those in L proteins of NNS RNA viruses belonging to the the order Mononegavirales. The structural model of the putative RABV PRNTase domain suggests that it possesses a large loop structure flanking the PRNTase motif B, which corresponds to a priming loop proposed for the VSV L protein Lyssavirus rabies
metabolism molecular mechanisms of RABV RNA biogenesis, overview. In the second step, the PRNTase domain in the VSV L protein transfers 5'-monophosphate-ended RNA (pRNA) from pppRNA (pRNA donor) to GDP (pRNA acceptor) through a covalent enzyme-(histidyl-N'')-pRNA (called L-pRNA) intermediate to generate GpppRNA. Roles of RABV replication proteins in transcription and replication, and unique RABV machineries required for mRNA capping and transcription initiation. Comparison of Rabies virus mechanism of mRNA capping with that of eukaryotic cells Lyssavirus rabies
additional information residues G1112 in motif A, T1170 in motif B, W1201 in motif C, H1241 and R1242 in motif D, and F1285 and Q1286 in motif E are identified as essential for the PRNTase activity of the RABV L protein. The RABV counterpart (H1241) of the VSV H1227 residue can be predicted to serve as a covalent pRNA attachment site for the putative L-pRNA intermediate formation. Structure and structure-function analysis, overview Lyssavirus rabies
physiological function the large (L) protein of the rabies virus (RABV) is a multifunctional RNA-dependent RNA-polymerase. Transcriptional control and mRNA capping are exerted by the GDP polyribonucleotidyltransferase domain of the rabies virus large protein. It catalyzes mRNA processing reactions, such as 5'-capping, cap methylation, and 3'-polyadenylation, in addition to RNA synthesis. The PRNTase domain in the VSV L protein transfers 5'-monophosphate-ended RNA (pRNA) from pppRNA (pRNA donor) to GDP (pRNA acceptor) through a covalent enzyme-(histidyl-N'')-pRNA (called L-pRNA) intermediate to generate GpppRNA, roles of the GDP polyribonucleotidyltransferase (PRNTase) domain of the rabies virus (RABV) large (L) protein in transcription initiation and pre-mRNA capping Lyssavirus rabies