[English] 日本語
Yorodumi
- EMDB-45296: EM map Of Respiratory Syncytial Virus Polymerase in complex with ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-45296
TitleEM map Of Respiratory Syncytial Virus Polymerase in complex with JNJ-2729
Map dataRSV Polymerase in complex with JNJ-2729
Sample
  • Complex: Respiratory syncytial virus polymerase in complex with non-nucleoside inhibitor
    • Protein or peptide: RNA-directed RNA polymerase L
    • Protein or peptide: Phosphoprotein
  • Ligand: (2S)-1,1,1-trifluoro-2-[5-fluoro-6-(4-fluorophenyl)-4-(2-hydroxypropan-2-yl)pyridin-2-yl]-3-[(4M)-4-(8-methoxyquinolin-6-yl)-1H-1,2,3-triazol-1-yl]propan-2-ol
KeywordsNon-Nucleoside Inhibitor / complex / Polymerase / RSV / VIRAL PROTEIN / TRANSFERASE-INHIBITOR complex
Function / homology
Function and homology information


NNS virus cap methyltransferase / Respiratory syncytial virus genome transcription / GDP polyribonucleotidyltransferase / Translation of respiratory syncytial virus mRNAs / negative stranded viral RNA replication / Respiratory syncytial virus genome replication / RSV-host interactions / Assembly and release of respiratory syncytial virus (RSV) virions / Maturation of hRSV A proteins / Respiratory syncytial virus (RSV) attachment and entry ...NNS virus cap methyltransferase / Respiratory syncytial virus genome transcription / GDP polyribonucleotidyltransferase / Translation of respiratory syncytial virus mRNAs / negative stranded viral RNA replication / Respiratory syncytial virus genome replication / RSV-host interactions / Assembly and release of respiratory syncytial virus (RSV) virions / Maturation of hRSV A proteins / Respiratory syncytial virus (RSV) attachment and entry / Hydrolases; Acting on acid anhydrides; In phosphorus-containing anhydrides / viral life cycle / virion component / symbiont-mediated suppression of host NF-kappaB cascade / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / RNA-directed RNA polymerase / RNA-dependent RNA polymerase activity / GTPase activity / ATP binding / metal ion binding
Similarity search - Function
Phosphoprotein, pneumoviral / Pneumovirus phosphoprotein / RNA-directed RNA polymerase L methyltransferase domain, rhabdovirus / Virus-capping methyltransferase, MT domain / RNA-directed RNA polymerase, paramyxovirus / Mononegavirales RNA-directed RNA polymerase catalytic domain / Mononegavirus L protein 2-O-ribose methyltransferase / Mononegavirales mRNA-capping domain V / RNA-directed RNA polymerase L, C-terminal / Mononegavirales RNA dependent RNA polymerase ...Phosphoprotein, pneumoviral / Pneumovirus phosphoprotein / RNA-directed RNA polymerase L methyltransferase domain, rhabdovirus / Virus-capping methyltransferase, MT domain / RNA-directed RNA polymerase, paramyxovirus / Mononegavirales RNA-directed RNA polymerase catalytic domain / Mononegavirus L protein 2-O-ribose methyltransferase / Mononegavirales mRNA-capping domain V / RNA-directed RNA polymerase L, C-terminal / Mononegavirales RNA dependent RNA polymerase / Mononegavirales mRNA-capping region V / RdRp of negative ssRNA viruses with non-segmented genomes catalytic domain profile. / Mononegavirus L protein 2'-O-ribose methyltransferase domain profile.
Similarity search - Domain/homology
Phosphoprotein / RNA-directed RNA polymerase L
Similarity search - Component
Biological speciesHuman respiratory syncytial virus A2
Methodsingle particle reconstruction / cryo EM / Resolution: 3.24 Å
AuthorsYin Y / Tran MT / Yu X / Jonckers T
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: ACS Med Chem Lett / Year: 2024
Title: Structure-Activity Relationship of Oxacyclo- and Triazolo-Containing Respiratory Syncytial Virus Polymerase Inhibitors.
Authors: Minh T Tran / Sandrine Grosse / Rodrigo J Carbajo / Edgar Jacoby / Yanting Yin / Xiaodi Yu / Carol Martinez / Bart Stoops / Ludwig Cooymans / Lili Hu / Ferdinand H Lutter / Serge Pieters / ...Authors: Minh T Tran / Sandrine Grosse / Rodrigo J Carbajo / Edgar Jacoby / Yanting Yin / Xiaodi Yu / Carol Martinez / Bart Stoops / Ludwig Cooymans / Lili Hu / Ferdinand H Lutter / Serge Pieters / Eric Tan / Jesus Alcázar / Dirk Roymans / Herman van Vlijmen / Peter Rigaux / Sujata Sharma / Tim H M Jonckers /
Abstract: Despite the availability of medicines preventing respiratory syncytial virus (RSV) infection, post-exposure treatment options are needed for addressing patient's needs. RSV non-nucleoside polymerase ...Despite the availability of medicines preventing respiratory syncytial virus (RSV) infection, post-exposure treatment options are needed for addressing patient's needs. RSV non-nucleoside polymerase inhibitors (NNI) have emerged as a promising asset for which our group previously disclosed JNJ-8003 with potent antiviral activity and pronounced efficacy. In this work, a structural-guided design to modify the linker vector of JNJ-8003 resulted in the identification of 2-oxacyclo pyridine-containing derivatives whose various ring closing strategies are described. In addition, bioisosteric replacement of an amide bond with triazole retained potency, and cryo-electron microscopy (cryo-EM) confirmed binding in the capping domain. Subsequent NMR conformational analysis suggested a correlation between the potency and conformations. Our efforts have fulfilled the aim of identifying linker modifications with maintained biological activity while enriching structural diversity and allowing modulations of other parameters.
History
DepositionJun 11, 2024-
Header (metadata) releaseJan 8, 2025-
Map releaseJan 8, 2025-
UpdateJan 8, 2025-
Current statusJan 8, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_45296.png

Downloads & links

-
Map

FileDownload / File: emd_45296.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationRSV Polymerase in complex with JNJ-2729
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 320 pix.
= 265.6 Å		0.83 Å/pix.
x 320 pix.
= 265.6 Å		0.83 Å/pix.
x 320 pix.
= 265.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0131
Minimum - Maximum-0.06000608 - 0.08709614
Average (Standard dev.)0.0000644502 (±0.0021580616)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 265.6 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_45296_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_45296_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Respiratory syncytial virus polymerase in complex with non-nucleo...

EntireName: Respiratory syncytial virus polymerase in complex with non-nucleoside inhibitor
Components
  • Complex: Respiratory syncytial virus polymerase in complex with non-nucleoside inhibitor
    • Protein or peptide: RNA-directed RNA polymerase L
    • Protein or peptide: Phosphoprotein
  • Ligand: (2S)-1,1,1-trifluoro-2-[5-fluoro-6-(4-fluorophenyl)-4-(2-hydroxypropan-2-yl)pyridin-2-yl]-3-[(4M)-4-(8-methoxyquinolin-6-yl)-1H-1,2,3-triazol-1-yl]propan-2-ol

-
Supramolecule #1: Respiratory syncytial virus polymerase in complex with non-nucleo...

SupramoleculeName: Respiratory syncytial virus polymerase in complex with non-nucleoside inhibitor
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Human respiratory syncytial virus A2

-
Macromolecule #1: RNA-directed RNA polymerase L

MacromoleculeName: RNA-directed RNA polymerase L / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: RNA-directed RNA polymerase
Source (natural)Organism: Human respiratory syncytial virus A2
Molecular weightTheoretical: 254.48275 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MGSWSHPQFE KGSGSGSSWS HPQFEKGSGS LVPRGSMDPI INGNSANVYL TDSYLKGVIS FSECNALGSY IFNGPYLKND YTNLISRQN PLIEHMNLKK LNITQSLISK YHKGEIKLEE PTYFQSLLMT YKSMTSSEQI ATTNLLKKII RRAIEISDVK V YAILNKLG ...String:
MGSWSHPQFE KGSGSGSSWS HPQFEKGSGS LVPRGSMDPI INGNSANVYL TDSYLKGVIS FSECNALGSY IFNGPYLKND YTNLISRQN PLIEHMNLKK LNITQSLISK YHKGEIKLEE PTYFQSLLMT YKSMTSSEQI ATTNLLKKII RRAIEISDVK V YAILNKLG LKEKDKIKSN NGQDEDNSVI TTIIKDDILS AVKDNQSHLK ADKNHSTKQK DTIKTTLLKK LMCSMQHPPS WL IHWFNLY TKLNNILTQY RSNEVKNHGF TLIDNQTLSG FQFILNQYGC IVYHKELKRI TVTTYNQFLT WKDISLSRLN VCL ITWISN CLNTLNKSLG LRCGFNNVIL TQLFLYGDCI LKLFHNEGFY IIKEVEGFIM SLILNITEED QFRKRFYNSM LNNI TDAAN KAQKNLLSRV CHTLLDKTVS DNIINGRWII LLSKFLKLIK LAGDNNLNNL SELYFLFRIF GHPMVDERQA MDAVK INCN ETKFYLLSSL SMLRGAFIYR IIKGFVNNYN RWPTLRNAIV LPLRWLTYYK LNTYPSLLEL TERDLIVLSG LRFYRE FRL PKKVDLEMII NDKAISPPKN LIWTSFPRNY MPSHIQNYIE HEKLKFSESD KSRRVLEYYL RDNKFNECDL YNCVVNQ SY LNNPNHVVSL TGKERELSVG RMFAMQPGMF RQVQILAEKM IAENILQFFP ESLTRYGDLE LQKILELKAG ISNKSNRY N DNYNNYISKC SIITDLSKFN QAFRYETSCI CSDVLDELHG VQSLFSWLHL TIPHVTIICT YRHAPPYIGD HIVDLNNVD EQSGLYRYHM GGIEGWCQKL WTIEAISLLD LISLKGKFSI TALINGDNQS IDISKPIRLM EGQTHAQADY LLALNSLKLL YKEYAGIGH KLKGTETYIS RDMQFMSKTI QHNGVYYPAS IKKVLRVGPW INTILDDFKV SLESIGSLTQ ELEYRGESLL C SLIFRNVW LYNQIALQLK NHALCNNKLY LDILKVLKHL KTFFNLDNID TALTLYMNLP MLFGGGDPNL LYRSFYRRTP DF LTEAIVH SVFILSYYTN HDLKDKLQDL SDDRLNKFLT CIITFDKNPN AEFVTLMRDP QALGSERQAK ITSEINRLAV TEV LSTAPN KIFSKSAQHY TTTEIDLNDI MQNIEPTYPH GLRVVYESLP FYKAEKIVNL ISGTKSITNI LEKTSAIDLT DIDR ATEMM RKNITLLIRI LPLDCNRDKR EILSMENLSI TELSKYVRER SWSLSNIVGV TSPSIMYTMD IKYTTSTISS GIIIE KYNV NSLTRGERGP TKPWVGSSTQ EKKTMPVYNR QVLTKKQRDQ IDLLAKLDWV YASIDNKDEF MEELSIGTLG LTYEKA KKL FPQYLSVNYL HRLTVSSRPC EFPASIPAYR TTNYHFDTSP INRILTEKYG DEDIDIVFQN CISFGLSLMS VVEQFTN VC PNRIILIPKL NEIHLMKPPI FTGDVDIHKL KQVIQKQHMF LPDKISLTQY VELFLSNKTL KSGSHVNSNL ILAHKISD Y FHNTYILSTN LAGHWILIIQ LMKDSKGIFE KDWGEGYITD HMFINLKVFF NAYKTYLLCF HKGYGKAKLE CDMNTSDLL CVLELIDSSY WKSMSKVFLE QKVIKYILSQ DASLHRVKGC HSFKLWFLKR LNVAEFTVCP WVVNIDYHPT HMKAILTYID LVRMGLINI DRIHIKNKHK FNDEFYTSNL FYINYNFSDN THLLTKHIRI ANSELENNYN KLYHPTPETL ENILANPIKS N DKKTLNDY CIGKNVDSIM LPLLSNKKLI KSSAMIRTNY SKQDLYNLFP MVVIDRIIDH SGNTAKSNQL YTTTSHQISL VH NSTSLYC MLPWHHINRF NFVFSSTGCK ISIEYILKDL KIKDPNCIAF IGEGAGNLLL RTVVELHPDI RYIYRSLKDC NDH SLPIEF LRLYNGHINI DYGENLTIPA TDATNNIHWS YLHIKFAEPI SLFVCDAELS VTVNWSKIII EWSKHVRKCK YCSS VNKCM LIVKYHAQDD IDFKLDNITI LKTYVCLGSK LKGSEVYLVL TIGPANIFPV FNVVQNAKLI LSRTKNFIMP KKADK ESID ANIKSLIPFL CYPITKKGIN TALSKLKSVV SGDILSYSIA GRNEVFSNKL INHKHMNILK WFNHVLNFRS TELNYN HLY MVESTYPYLS ELLNSLTTNE LKKLIKITGS LLYNFHNE

UniProtKB: RNA-directed RNA polymerase L

-
Macromolecule #2: Phosphoprotein

MacromoleculeName: Phosphoprotein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Human respiratory syncytial virus A2
Molecular weightTheoretical: 29.062895 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MEKFAPEFHG EDANNRATKF LESIKGKFTS PKDPKKKDSI ISVNSIDIEV TKESPITSNS TIINPTNETD DTAGNKPNYQ RKPLVSFKE DPTPSDNPFS KLYKETIETF DNNEEESSYS YEEINDQTND NITARLDRID EKLSEILGML HTLVVASAGP T SARDGIRD ...String:
MEKFAPEFHG EDANNRATKF LESIKGKFTS PKDPKKKDSI ISVNSIDIEV TKESPITSNS TIINPTNETD DTAGNKPNYQ RKPLVSFKE DPTPSDNPFS KLYKETIETF DNNEEESSYS YEEINDQTND NITARLDRID EKLSEILGML HTLVVASAGP T SARDGIRD AMIGLREEMI EKIRTEALMT NDRLEAMARL RNEESEKMAK DTSDEVSLNP TSEKLNNLLE GNDSDNDLSL ED FKGENKY FQGHHHHHH

UniProtKB: Phosphoprotein

-
Macromolecule #3: (2S)-1,1,1-trifluoro-2-[5-fluoro-6-(4-fluorophenyl)-4-(2-hydroxyp...

MacromoleculeName: (2S)-1,1,1-trifluoro-2-[5-fluoro-6-(4-fluorophenyl)-4-(2-hydroxypropan-2-yl)pyridin-2-yl]-3-[(4M)-4-(8-methoxyquinolin-6-yl)-1H-1,2,3-triazol-1-yl]propan-2-ol
type: ligand / ID: 3 / Number of copies: 1 / Formula: A1AWZ
Molecular weightTheoretical: 585.525 Da

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.368 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 1.4000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.24 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 267890
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

+
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