+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23109 | |||||||||
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Title | SARS-CoV-2 RdRp in complex with 4 Remdesivir monophosphate | |||||||||
Map data | SARS-CoV-2 RdRp in complex with 4 Remdesivir monophosphate | |||||||||
Sample |
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Keywords | VIRAL PROTEIN / VIRAL PROTEIN-RNA complex | |||||||||
Function / homology | Function and homology information protein guanylyltransferase activity / RNA endonuclease activity, producing 3'-phosphomonoesters / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs ...protein guanylyltransferase activity / RNA endonuclease activity, producing 3'-phosphomonoesters / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / Maturation of replicase proteins / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs / Translation of Replicase and Assembly of the Replication Transcription Complex / TRAF3-dependent IRF activation pathway / Replication of the SARS-CoV-2 genome / snRNP Assembly / double membrane vesicle viral factory outer membrane / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / 5'-3' DNA helicase activity / SARS coronavirus main proteinase / 3'-5'-RNA exonuclease activity / host cell endoplasmic reticulum-Golgi intermediate compartment / host cell endosome / symbiont-mediated suppression of host toll-like receptor signaling pathway / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / omega peptidase activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / SARS-CoV-2 modulates host translation machinery / mRNA (guanine-N7)-methyltransferase / host cell Golgi apparatus / methyltransferase cap1 / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / viral protein processing / lyase activity / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / induction by virus of host autophagy / copper ion binding / cysteine-type endopeptidase activity / RNA-directed RNA polymerase / viral RNA genome replication / virus-mediated perturbation of host defense response / RNA-dependent RNA polymerase activity / DNA-templated transcription / lipid binding / host cell nucleus / SARS-CoV-2 activates/modulates innate and adaptive immune responses / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.89 Å | |||||||||
Authors | Bravo JPK / Taylor DW | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Mol Cell / Year: 2021 Title: Remdesivir is a delayed translocation inhibitor of SARS-CoV-2 replication. Authors: Jack P K Bravo / Tyler L Dangerfield / David W Taylor / Kenneth A Johnson / Abstract: Remdesivir is a nucleoside analog approved by the US FDA for treatment of COVID-19. Here, we present a 3.9-Å-resolution cryo-EM reconstruction of a remdesivir-stalled RNA-dependent RNA polymerase ...Remdesivir is a nucleoside analog approved by the US FDA for treatment of COVID-19. Here, we present a 3.9-Å-resolution cryo-EM reconstruction of a remdesivir-stalled RNA-dependent RNA polymerase complex, revealing full incorporation of 3 copies of remdesivir monophosphate (RMP) and a partially incorporated fourth RMP in the active site. The structure reveals that RMP blocks RNA translocation after incorporation of 3 bases following RMP, resulting in delayed chain termination, which can guide the rational design of improved antiviral drugs. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23109.map.gz | 1 MB | EMDB map data format | |
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Header (meta data) | emd-23109-v30.xml emd-23109.xml | 15 KB 15 KB | Display Display | EMDB header |
Images | emd_23109.png | 126.4 KB | ||
Filedesc metadata | emd-23109.cif.gz | 6.3 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23109 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23109 | HTTPS FTP |
-Validation report
Summary document | emd_23109_validation.pdf.gz | 408 KB | Display | EMDB validaton report |
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Full document | emd_23109_full_validation.pdf.gz | 407.5 KB | Display | |
Data in XML | emd_23109_validation.xml.gz | 4.3 KB | Display | |
Data in CIF | emd_23109_validation.cif.gz | 4.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23109 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23109 | HTTPS FTP |
-Related structure data
Related structure data | 7l1fMC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23109.map.gz / Format: CCP4 / Size: 3.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | SARS-CoV-2 RdRp in complex with 4 Remdesivir monophosphate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : SARS-CoV-2 RdRp complex with template:primer and four RMP
Entire | Name: SARS-CoV-2 RdRp complex with template:primer and four RMP |
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Components |
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-Supramolecule #1: SARS-CoV-2 RdRp complex with template:primer and four RMP
Supramolecule | Name: SARS-CoV-2 RdRp complex with template:primer and four RMP type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: RNA-directed RNA polymerase, Non-structural protein 8, Non-struct...
Supramolecule | Name: RNA-directed RNA polymerase, Non-structural protein 8, Non-structural protein 7 type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
-Supramolecule #3: RNA
Supramolecule | Name: RNA / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #4-#5 |
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-Macromolecule #1: RNA-directed RNA polymerase
Macromolecule | Name: RNA-directed RNA polymerase / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: RNA-directed RNA polymerase |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 103.372164 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: YRAFDIYNDK VAGFAKFLKT NCCRFQEKDE DDNLIDSYFV VKRHTFSNYQ HEETIYNLLK DCPAVAKHDF FKFRIDGDMV PHISRQRLT KYTMADLVYA LRHFDEGNCD TLKEILVTYN CCDDDYFNKK DWYDFVENPD ILRVYANLGE RVRQALLKTV Q FCDAMRNA ...String: YRAFDIYNDK VAGFAKFLKT NCCRFQEKDE DDNLIDSYFV VKRHTFSNYQ HEETIYNLLK DCPAVAKHDF FKFRIDGDMV PHISRQRLT KYTMADLVYA LRHFDEGNCD TLKEILVTYN CCDDDYFNKK DWYDFVENPD ILRVYANLGE RVRQALLKTV Q FCDAMRNA GIVGVLTLDN QDLNGNWYDF GDFIQTTPGS GVPVVDSYYS LLMPILTLTR ALTAESHVDT DLTKPYIKWD LL KYDFTEE RLKLFDRYFK YWDQTYHPNC VNCLDDRCIL HCANFNVLFS TVFPPTSFGP LVRKIFVDGV PFVVSTGYHF REL GVVHNQ DVNLHSSRLS FKELLVYAAD PAMHAASGNL LLDKRTTCFS VAALTNNVAF QTVKPGNFNK DFYDFAVSKG FFKE GSSVE LKHFFFAQDG NAAISDYDYY RYNLPTMCDI RQLLFVVEVV DKYFDCYDGG CINANQVIVN NLDKSAGFPF NKWGK ARLY YDSMSYEDQD ALFAYTKRNV IPTITQMNLK YAISAKNRAR TVAGVSICST MTNRQFHQKL LKSIAATRGA TVVIGT SKF YGGWHNMLKT VYSDVENPHL MGWDYPKCDR AMPNMLRIMA SLVLARKHTT CCSLSHRFYR LANECAQVLS EMVMCGG SL YVKPGGTSSG DATTAYANSV FNICQAVTAN VNALLSTDGN KIADKYVRNL QHRLYECLYR NRDVDTDFVN EFYAYLRK H FSMMILSDDA VVCFNSTYAS QGLVASIKNF KSVLYYQNNV FMSEAKCWTE TDLTKGPHEF CSQHTMLVKQ GDDYVYLPY PDPSRILGAG CFVDDIVKTD GTLMIERFVS LAIDAYPLTK HPNQEYADVF HLYLQYIRKL HDELTGHMLD MYSVMLTNDN TSRYWEPEF YEAMYTPHT UniProtKB: Replicase polyprotein 1ab |
-Macromolecule #2: Non-structural protein 8
Macromolecule | Name: Non-structural protein 8 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 12.644559 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: DKRAKVTSAM QTMLFTMLRK LDNDALNNII NNARDGCVPL NIIPLTTAAK LMVVIPDYNT YKNTCDGTTF TYASALWEIQ QVVDADSKI VQLSEISMDN SPNLAWPLIV TALRA UniProtKB: Replicase polyprotein 1ab |
-Macromolecule #3: Non-structural protein 7
Macromolecule | Name: Non-structural protein 7 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 7.001255 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: KMSDVKCTSV VLLSVLQQLR VESSSKLWAQ CVQLHNDILL AKDTTEAFEK MVSLLSVLLS MQG UniProtKB: Replicase polyprotein 1ab |
-Macromolecule #4: RNA (5'-R(P*CP*UP*AP*AP*GP*AP*AP*GP*CP*UP*AP*UP*U*(F86)*(F86)*(F8...
Macromolecule | Name: RNA (5'-R(P*CP*UP*AP*AP*GP*AP*AP*GP*CP*UP*AP*UP*U*(F86)*(F86)*(F86)*(F86))-3') type: rna / ID: 4 / Number of copies: 1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 5.539421 KDa |
Sequence | String: CUAAGAAGCU AUU(F86)(F86)(F86)(F86) |
-Macromolecule #5: RNA (5'-R(P*AP*UP*UP*UP*UP*AP*AP*UP*AP*GP*CP*UP*UP*CP*UP*UP*AP*G)-3')
Macromolecule | Name: RNA (5'-R(P*AP*UP*UP*UP*UP*AP*AP*UP*AP*GP*CP*UP*UP*CP*UP*UP*AP*G)-3') type: rna / ID: 5 / Number of copies: 1 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 5.657339 KDa |
Sequence | String: AUUUUAAUAG CUUCUUAG |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: NONE |
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Final reconstruction | Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.89 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 116748 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |