Use my Search Websuite to scan PubMed, PMCentral, Journal Hosts and Journal Archives, FullText. Kick-your-searchterm to multiple Engines kick-your-query now !>

A dictionary by aggregated review articles of nephrology, medicine and the life sciences Your one-stop-run pathway from word to the immediate pdf of peer-reviewed on-topic knowledge.

10.1093/nar/gkab677 http://scihub22266oqcxt.onion/10.1093/nar/gkab677 34352100!8385902!34352100     free     free     free Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 213.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nucleic+Acids+Res 2021 ; 49 (15): 8822-8835 Nephropedia Template TP {{tp|p=34352100|t=2021. NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain |pdf=|usr=}}{{34352100}} gab.com Text NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain JO: Nucleic Acids Res http://www.kidney.de/pget.php?&tw=1&pmid=34352100 #FOAvip The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) contains two active sites that catalyze nucleotidyl-monophosphate transfer (NMPylation). Mechanistic studies and drug discovery have focused on RNA synthesis by the highly conserved RdRp. The second active site, which resides in a Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain, is poorly characterized, but both catalytic reactions are essential for viral replication. One study showed that NiRAN transfers NMP to the first residue of RNA-binding protein nsp9; another reported a structure of nsp9 containing two additional N-terminal residues bound to the NiRAN active site but observed NMP transfer to RNA instead. We show that SARS-CoV-2 RdRp NMPylates the native but not the extended nsp9. Substitutions of the invariant NiRAN residues abolish NMPylation, whereas substitution of a catalytic RdRp Asp residue does not. NMPylation can utilize diverse nucleotide triphosphates, including remdesivir triphosphate, is reversible in the presence of pyrophosphate, and is inhibited by nucleotide analogs and bisphosphonates, suggesting a path for rational design of NiRAN inhibitors. We reconcile these and existing findings using a new model in which nsp9 remodels both active sites to alternately support initiation of RNA synthesis by RdRp or subsequent capping of the product RNA by the NiRAN domain. Twit Text FOAVip NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain ????Nucleic Acids Res http://www.kidney.de/pget.php?&tw=1&pmid=34352100 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=34352100 #FOAvip English Wikipedia <ref>{{Cite pmid|34352100}}</ref> NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain #MMPMID34352100 Wang B; Svetlov D; Artsimovitch I Nucleic Acids Res 2021[Sep]; 49 (15): 8822-8835 PMID34352100show ga The catalytic subunit of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) contains two active sites that catalyze nucleotidyl-monophosphate transfer (NMPylation). Mechanistic studies and drug discovery have focused on RNA synthesis by the highly conserved RdRp. The second active site, which resides in a Nidovirus RdRp-Associated Nucleotidyl transferase (NiRAN) domain, is poorly characterized, but both catalytic reactions are essential for viral replication. One study showed that NiRAN transfers NMP to the first residue of RNA-binding protein nsp9; another reported a structure of nsp9 containing two additional N-terminal residues bound to the NiRAN active site but observed NMP transfer to RNA instead. We show that SARS-CoV-2 RdRp NMPylates the native but not the extended nsp9. Substitutions of the invariant NiRAN residues abolish NMPylation, whereas substitution of a catalytic RdRp Asp residue does not. NMPylation can utilize diverse nucleotide triphosphates, including remdesivir triphosphate, is reversible in the presence of pyrophosphate, and is inhibited by nucleotide analogs and bisphosphonates, suggesting a path for rational design of NiRAN inhibitors. We reconcile these and existing findings using a new model in which nsp9 remodels both active sites to alternately support initiation of RNA synthesis by RdRp or subsequent capping of the product RNA by the NiRAN domain. |*Protein Domains[MESH] |Amino Acid Sequence[MESH] |Catalytic Domain[MESH] |Coenzymes/metabolism[MESH] |Coronavirus RNA-Dependent RNA Polymerase/metabolism[MESH] |Diphosphates/pharmacology[MESH] |Diphosphonates/pharmacology[MESH] |Guanosine Triphosphate/metabolism[MESH] |Manganese[MESH] |Models, Molecular[MESH] |Nidovirales/chemistry/*enzymology[MESH] |Nucleotides/*metabolism[MESH] |RNA-Binding Proteins/*chemistry/*metabolism[MESH] |RNA-Dependent RNA Polymerase/antagonists & inhibitors/*chemistry/*metabolism[MESH] |SARS-CoV-2/*enzymology[MESH] |Uridine Triphosphate/metabolism[MESH]NMPylation and de-NMPylation of SARS-CoV-2 nsp9 by the NiRAN domain (epmc).pdf DeepDyve Pubget Overpricing