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 (Comment) | Organism |
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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 | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Lyssavirus rabies |
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] | - |
? | |
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 | UniProt | Comment | Textmining |
---|---|---|---|
Lyssavirus rabies | P11213 | RABV | - |
Lyssavirus rabies Pasteur vaccins | P11213 | RABV | - |
Lyssavirus rabies PV | P11213 | RABV | - |
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 | ? | - |
- |
|
additional information | structure-function analysis, and substrate binding structure analysis, overview | Lyssavirus rabies PV | ? | - |
- |
|
additional information | structure-function analysis, and substrate binding structure analysis, overview | Lyssavirus rabies Pasteur vaccins | ? | - |
- |
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 | Comment | Organism |
---|---|---|
More | cf. EC 2.7.7.48 | Lyssavirus rabies |
mRNA capping enzyme | - |
Lyssavirus rabies |
PRNTase | - |
Lyssavirus rabies |
rabies virus large protein | - |
Lyssavirus rabies |
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 |