[English] 日本語
Yorodumi
- PDB-8frj: Structure of nsp14 N7-MethylTransferase domain fused with TELSAM ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8frj
TitleStructure of nsp14 N7-MethylTransferase domain fused with TELSAM bound to SGC0946
ComponentsTranscription factor ETV6,Guanine-N7 methyltransferase nsp14 chimera
KeywordsVIRAL PROTEIN / N7-guanine methyl transferase / SARS-CoV-2 / nsp14
Function / homology
Function and homology information


Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / mesenchymal cell apoptotic process / vitellogenesis / hematopoietic stem cell proliferation / neurogenesis / Signaling by FLT3 fusion proteins / RNA polymerase II transcription regulatory region sequence-specific DNA binding / DNA-binding transcription repressor activity, RNA polymerase II-specific / protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism ...Signaling by membrane-tethered fusions of PDGFRA or PDGFRB / mesenchymal cell apoptotic process / vitellogenesis / hematopoietic stem cell proliferation / neurogenesis / Signaling by FLT3 fusion proteins / RNA polymerase II transcription regulatory region sequence-specific DNA binding / DNA-binding transcription repressor activity, RNA polymerase II-specific / protein guanylyltransferase activity / RNA endonuclease activity producing 3'-phosphomonoesters, hydrolytic mechanism / mRNA guanylyltransferase activity / 5'-3' RNA helicase activity / Lyases; Phosphorus-oxygen lyases / Assembly of the SARS-CoV-2 Replication-Transcription Complex (RTC) / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / Maturation of replicase proteins / TRAF3-dependent IRF activation pathway / ISG15-specific peptidase activity / Transcription of SARS-CoV-2 sgRNAs / snRNP Assembly / Translation of Replicase and Assembly of the Replication Transcription Complex / DNA-binding transcription activator activity, RNA polymerase II-specific / Replication of the SARS-CoV-2 genome / Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters / double membrane vesicle viral factory outer membrane / host cell endoplasmic reticulum-Golgi intermediate compartment / SARS coronavirus main proteinase / 5'-3' DNA helicase activity / 3'-5'-RNA exonuclease activity / host cell endosome / symbiont-mediated degradation of host mRNA / mRNA guanylyltransferase / symbiont-mediated suppression of host ISG15-protein conjugation / G-quadruplex RNA binding / symbiont-mediated suppression of host toll-like receptor signaling pathway / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity / omega peptidase activity / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / SARS-CoV-2 modulates host translation machinery / host cell Golgi apparatus / symbiont-mediated suppression of host NF-kappaB cascade / symbiont-mediated perturbation of host ubiquitin-like protein modification / DNA helicase / methyltransferase cap1 activity / ubiquitinyl hydrolase 1 / DNA-binding transcription factor activity, RNA polymerase II-specific / cysteine-type deubiquitinase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / cell differentiation / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / single-stranded RNA binding / regulation of autophagy / viral protein processing / lyase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / symbiont-mediated suppression of host gene expression / copper ion binding / protein domain specific binding / viral translational frameshifting / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / DNA-templated transcription / lipid binding / regulation of transcription by RNA polymerase II / chromatin / nucleolus / host cell nucleus / SARS-CoV-2 activates/modulates innate and adaptive immune responses / negative regulation of transcription by RNA polymerase II / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / nucleus / membrane / plasma membrane / cytosol
Similarity search - Function
SAM / Pointed domain / Pointed domain / Sterile alpha motif (SAM)/Pointed domain / Pointed (PNT) domain profile. / Transcription Factor, Ets-1 / Ets-domain signature 2. / Ets domain / ETS family / Ets-domain / Ets-domain profile. ...SAM / Pointed domain / Pointed domain / Sterile alpha motif (SAM)/Pointed domain / Pointed (PNT) domain profile. / Transcription Factor, Ets-1 / Ets-domain signature 2. / Ets domain / ETS family / Ets-domain / Ets-domain profile. / erythroblast transformation specific domain / Sterile alpha motif/pointed domain superfamily / DNA polymerase; domain 1 / RNA-dependent RNA polymerase, SARS-CoV-like / Nonstructural protein 14, betacoronavirus / NSP15, NendoU domain, coronavirus / Nonstructural protein 15, middle domain, alpha/betacoronavirus / Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus / NSP14, guanine-N7-methyltransferase domain, coronavirus / Coronavirus (CoV) guanine-N7-methyltransferase (N7-MTase) domain profile. / Coronavirus (CoV) Nsp15 N-terminal oligomerization domain profile. / NSP12 RNA-dependent RNA polymerase, coronavirus / : / Coronavirus Nsp12 RNA-dependent RNA polymerase (RdRp) domain profile. / Coronavirus Nsp12 Interface domain profile. / : / : / Coronavirus Nonstructural protein 13, 1B domain / Coronavirus Non-structural protein 13, zinc-binding domain / Coronavirus Nonstructural protein 13, stalk domain / Nidovirus 2-O-methyltransferase / Nidovirus 2'-O-methyltransferase (2'-O-MTase) domain profile. / Non-structural protein NSP15, N-terminal domain superfamily, coronavirus / Non-structural protein NSP15, middle domain superfamily / Coronavirus replicase NSP15, N-terminal oligomerization / Nonstructural protein 15, middle domain, coronavirus / Nonstructural protein 13, 1B domain, coronavirus / Coronavirus replicase NSP15, middle domain / Coronavirus replicase NSP15, N-terminal oligomerisation / Nidovirus 3'-5' exoribonuclease domain / Nidovirus 3'-5' exoribonuclease (ExoN) domain profile. / Non-structural protein NSP16, coronavirus-like / Non-structural protein 14, coronavirus / RNA polymerase, N-terminal, coronavirus / Coronavirus 2'-O-methyltransferase / Coronavirus proofreading exoribonuclease / Coronavirus RNA-dependent RNA polymerase, N-terminal / Nonstructural protein 13, zinc-binding domain, coronavirus-like / Coronaviridae zinc-binding (CV ZBD) domain profile. / Arterivirus Nsp11 N-terminal/Coronavirus NSP15 middle domain / Arterivirus Nsp11 N-terminal/coronavirus NSP15 middle (AV-Nsp11N/CoV-Nsp15M) domain profile. / Nidoviral uridylate-specific endoribonuclease (NendoU) domain profile. / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain / Nidovirus RdRp-associated nucleotidyl transferase (NiRAN) domain profile. / Endoribonuclease EndoU-like / NendoU domain, nidovirus / Coronavirus replicase NSP15, uridylate-specific endoribonuclease / : / Lipocalin signature. / DNA2/NAM7 helicase-like, C-terminal / AAA domain / (+) RNA virus helicase core domain / (+)RNA virus helicase core domain profile. / Non-structural protein NSP3, SUD-N (Mac2) domain, betacoronavirus / Sarbecovirus Nsp3c-N domain profile. / Non-structural protein NSP3, N-terminal, betacoronavirus / Polyprotein cleavage domain PL2pro superfamily, betacoronavirus / Non-structural protein NSP3, SUD-N (Mac2) domain superfamily, betacoronavirus / Betacoronavirus SUD-C domain / Betacoronavirus replicase NSP3, N-terminal / NSP1 globular domain superfamily, betacoronavirus / Non-structural protein 2, SARS-CoV-like / Betacoronavirus single-stranded poly(A) binding domain / Betacoronavirus Nsp3c-M domain profile. / NSP1, globular domain, betacoronavirus / Non-structural protein NSP3, SUD-M domain, betacoronavirus / Non-structural protein NSP3, SUD-M domain superfamily, betacoronavirus / NSP1, C-terminal domain, betacoronavirus / Betacoronavirus replicase NSP1 / Betacoronavirus (BetaCoV) Nsp1 C-terminal domain profile. / : / Betacoronavirus Nsp3e group 2-specific marker (G2M) domain profile. / Betacoronavirus Nsp3c-C domain profile. / Betacoronavirus Nsp3e nucleic acid-binding (NAB) domain profile. / DPUP/SUD, C-terminal, betacoronavirus / Non-structural protein NSP3, nucleic acid-binding domain, betacoronavirus / Non-structural protein NSP3A domain-like superfamily / Non-structural protein NSP3, nucleic acid-binding domain superfamily, betacoronavirus / Non-structural protein 6, betacoronavirus / Betacoronavirus nucleic acid-binding (NAB) / Papain-like viral protease, palm and finger domains, coronavirus / Papain-like protease, N-terminal domain superfamily, coronavirus / Carbamoyl-phosphate synthase subdomain signature 2. / Coronavirus replicase NSP2, N-terminal / : / Coronavirus replicase NSP2, C-terminal / Coronavirus (CoV) Nsp2 middle domain profile. / NSP1, globular domain, alpha/betacoronavirus / Coronavirus (CoV) Nsp1 globular domain profile. / Coronavirus (CoV) Nsp2 N-terminal domain profile.
Similarity search - Domain/homology
Chem-AW2 / Replicase polyprotein 1ab / Transcription factor ETV6
Similarity search - Component
Biological speciesSevere acute respiratory syndrome coronavirus 2
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.57 Å
AuthorsKottur, J. / Aggarwal, A.K.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Plos Pathog. / Year: 2023
Title: Structures of SARS-CoV-2 N7-methyltransferase with DOT1L and PRMT7 inhibitors provide a platform for new antivirals.
Authors: Kottur, J. / White, K.M. / Rodriguez, M.L. / Rechkoblit, O. / Quintana-Feliciano, R. / Nayar, A. / Garcia-Sastre, A. / Aggarwal, A.K.
History
DepositionJan 7, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 26, 2023Provider: repository / Type: Initial release
Revision 1.1Sep 27, 2023Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Transcription factor ETV6,Guanine-N7 methyltransferase nsp14 chimera
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,1233
Polymers35,4391
Non-polymers6842
Water6,954386
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)109.155, 109.155, 48.640
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number170
Space group name H-MP65
Space group name HallP65
Symmetry operation#1: x,y,z
#2: x-y,x,z+5/6
#3: y,-x+y,z+1/6
#4: -y,x-y,z+2/3
#5: -x+y,-x,z+1/3
#6: -x,-y,z+1/2

-
Components

#1: Protein Transcription factor ETV6,Guanine-N7 methyltransferase nsp14 chimera / ETS translocation variant 6 / ETS-related protein Tel1 / Tel / Non-structural protein 14 / nsp14 / ...ETS translocation variant 6 / ETS-related protein Tel1 / Tel / Non-structural protein 14 / nsp14 / Proofreading exoribonuclease nsp14 / ExoN


Mass: 35439.262 Da / Num. of mol.: 1 / Mutation: A4R, E67V, A77K
Source method: isolated from a genetically manipulated source
Details: Fusion protein containing TELSAM (uniprot P41212) and SARS-CoV-2 nsp14 N7-Methyl Transferase domain (P0DTD1)
Source: (gene. exp.) Severe acute respiratory syndrome coronavirus 2
Gene: ETV6, TEL, TEL1, rep, 1a-1b / Production host: Escherichia coli (E. coli)
References: UniProt: P41212, UniProt: P0DTD1, mRNA (guanine-N7)-methyltransferase, Hydrolases; Acting on ester bonds; Exoribonucleases producing 5'-phosphomonoesters
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-AW2 / 5-bromo-7-{5-[(3-{[(4-tert-butylphenyl)carbamoyl]amino}propyl)(propan-2-yl)amino]-5-deoxy-beta-D-ribofuranosyl}-7H-pyrrolo[2,3-d]pyrimidin-4-amine


Mass: 618.566 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H40BrN7O4 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 386 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.36 Å3/Da / Density % sol: 47.89 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 11-17% Reagent Alcohol, 0.1-0.3M Lithium Sulfate and 0.1M Sodium Citrate pH 5.5
PH range: 5.1-6.0

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSLS-II / Beamline: 17-ID-2 / Wavelength: 0.979338 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Dec 1, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979338 Å / Relative weight: 1
ReflectionResolution: 1.57→54.595 Å / Num. obs: 31718 / % possible obs: 94.3 % / Redundancy: 10.2 % / Biso Wilson estimate: 20.91 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.105 / Rpim(I) all: 0.05 / Rrim(I) all: 0.116 / Net I/σ(I): 10.7
Reflection shellResolution: 1.57→1.711 Å / Rmerge(I) obs: 1.116 / Mean I/σ(I) obs: 1.6 / Num. unique obs: 1588 / CC1/2: 0.618 / Rpim(I) all: 0.602

-
Processing

Software
NameVersionClassification
PHENIX1.20rc3_4406refinement
XDSFeb 5, 2021 (BUILT 20210323)data reduction
Aimless0.7.4data scaling
STARANISO2.3.13 (20190907)data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.57→36.31 Å / SU ML: 0.1479 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 27.2803
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2043 1575 4.97 %
Rwork0.1698 30141 -
obs0.1715 31716 67.75 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 27.79 Å2
Refinement stepCycle: LAST / Resolution: 1.57→36.31 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2103 0 41 386 2530
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01032277
X-RAY DIFFRACTIONf_angle_d0.93383118
X-RAY DIFFRACTIONf_chiral_restr0.0592333
X-RAY DIFFRACTIONf_plane_restr0.0082395
X-RAY DIFFRACTIONf_dihedral_angle_d7.1232338
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.57-1.620.512690.3718232X-RAY DIFFRACTION5.69
1.62-1.670.4017300.3126698X-RAY DIFFRACTION17.44
1.67-1.740.2871630.25281087X-RAY DIFFRACTION27.12
1.74-1.820.2362610.22861589X-RAY DIFFRACTION39.29
1.82-1.920.23621420.20162388X-RAY DIFFRACTION59.63
1.92-2.040.23131960.20563851X-RAY DIFFRACTION95.58
2.04-2.190.21192030.17724036X-RAY DIFFRACTION99.74
2.19-2.410.2082030.16774016X-RAY DIFFRACTION99.55
2.41-2.760.18522280.17074027X-RAY DIFFRACTION99.7
2.76-3.480.21621960.16334094X-RAY DIFFRACTION99.93
3.48-36.310.1882440.15284123X-RAY DIFFRACTION99.93
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
11.491168303030.011416198750.01400884143482.275737711770.378692422270.675288291273-0.0645964378995-0.02868673133320.0781219572273-0.0537235447799-0.06850340615720.154586829013-0.00939170558247-0.2654899304470.06479277962820.125781767217-0.0114114906131-0.01170326599110.195080297848-0.07337689705190.296346120007-20.6205566521-6.68844668101-3.03449326581
21.049278086880.0175865128551-0.3385420457320.7127182322970.005106751136871.714975512060.01112959009140.05559114111510.00632043515698-0.01677643343620.03194542663610.007969392132960.09278175760490.127884347855-0.002546372011150.05680427909630.0544157513154-0.004345863439620.102689401625-0.01280327202740.0876484882032-37.4417205194-35.90260304874.44707087415
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11chain 'A' and (resid 5 through 81 )5 - 811 - 77
22chain 'A' and (resid 300 through 526 )300 - 52678 - 264

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more