[English] 日本語
Yorodumi
- PDB-4ncm: Influenza polymerase basic protein 2 (PB2) bound to a small-molec... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4ncm
TitleInfluenza polymerase basic protein 2 (PB2) bound to a small-molecule inhibitor
ComponentsPolymerase basic protein 2
KeywordsTRANSCRIPTION/TRANSCRIPTION INHIBITOR / RNA-dependent RNA polymerase / transcription / PB2 subunit / influenza virus / cap-binding domain / TRANSCRIPTION-TRANSCRIPTION INHIBITOR complex
Function / homology
Function and homology information


cap snatching / symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity / host cell mitochondrion / 7-methylguanosine mRNA capping / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / virion component / viral RNA genome replication / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription ...cap snatching / symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity / host cell mitochondrion / 7-methylguanosine mRNA capping / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / virion component / viral RNA genome replication / RNA-dependent RNA polymerase activity / virus-mediated perturbation of host defense response / DNA-templated transcription / host cell nucleus / RNA binding
Similarity search - Function
Influenza RNA-dependent RNA polymerase subunit PB2 / PB2, C-terminal / : / : / : / : / : / Influenza RNA polymerase PB2 N-terminal region / Influenza RNA polymerase PB2 second domain / Influenza RNA polymerase PB2 middle domain ...Influenza RNA-dependent RNA polymerase subunit PB2 / PB2, C-terminal / : / : / : / : / : / Influenza RNA polymerase PB2 N-terminal region / Influenza RNA polymerase PB2 second domain / Influenza RNA polymerase PB2 middle domain / Influenza RNA polymerase PB2 6th domain / Influenza RNA polymerase PB2 C-terminal domain / : / Influenza RNA polymerase PB2 CAP binding domain / : / Influenza RNA polymerase PB2 helical domain
Similarity search - Domain/homology
Chem-704 / Polymerase basic protein 2
Similarity search - Component
Biological speciesInfluenza A virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.82 Å
AuthorsJacobs, M.D.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2.
Authors: Clark, M.P. / Ledeboer, M.W. / Davies, I. / Byrn, R.A. / Jones, S.M. / Perola, E. / Tsai, A. / Jacobs, M. / Nti-Addae, K. / Bandarage, U.K. / Boyd, M.J. / Bethiel, R.S. / Court, J.J. / Deng, ...Authors: Clark, M.P. / Ledeboer, M.W. / Davies, I. / Byrn, R.A. / Jones, S.M. / Perola, E. / Tsai, A. / Jacobs, M. / Nti-Addae, K. / Bandarage, U.K. / Boyd, M.J. / Bethiel, R.S. / Court, J.J. / Deng, H. / Duffy, J.P. / Dorsch, W.A. / Farmer, L.J. / Gao, H. / Gu, W. / Jackson, K. / Jacobs, D.H. / Kennedy, J.M. / Ledford, B. / Liang, J. / Maltais, F. / Murcko, M. / Wang, T. / Wannamaker, M.W. / Bennett, H.B. / Leeman, J.R. / McNeil, C. / Taylor, W.P. / Memmott, C. / Jiang, M. / Rijnbrand, R. / Bral, C. / Germann, U. / Nezami, A. / Zhang, Y. / Salituro, F.G. / Bennani, Y.L. / Charifson, P.S.
History
DepositionOct 24, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 30, 2014Provider: repository / Type: Initial release
Revision 1.1Aug 6, 2014Group: Database references
Revision 1.2Aug 27, 2014Group: Database references
Revision 1.3Sep 20, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Polymerase basic protein 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)19,5372
Polymers19,1741
Non-polymers3631
Water48627
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)82.100, 82.100, 54.360
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number170
Space group name H-MP65

-
Components

#1: Protein Polymerase basic protein 2 / RNA-directed RNA polymerase subunit P3


Mass: 19174.324 Da / Num. of mol.: 1 / Fragment: CAP-BINDING DOMAIN / Mutation: R389K
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Influenza A virus / Strain: A/Victoria/3/1975 H3N2 / Gene: PB2, polymerase basic protein 2 PB2 / Plasmid: pET28b.1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)pLysS / References: UniProt: P31345
#2: Chemical ChemComp-704 / N~2~-[2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl]-N,N-dimethyl-L-alaninamide


Mass: 362.789 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C16H16ClFN6O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 27 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.76 Å3/Da / Density % sol: 55.41 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 4.7
Details: 0.7 uL of protein solution (9.7 mg/mL protein, 50 mM Tris buffer pH 8, 200 mM sodium chloride, 2 mM dithiothreitol, 5 mM m7GTP) was mixed with 0.35 uL Hampton Research Silver Bullet ...Details: 0.7 uL of protein solution (9.7 mg/mL protein, 50 mM Tris buffer pH 8, 200 mM sodium chloride, 2 mM dithiothreitol, 5 mM m7GTP) was mixed with 0.35 uL Hampton Research Silver Bullet screening reagent #36. This mixture was combined with 0.35 uL of well solution (approximately 1.3 M sodium formate, 100 mM sodium citrate buffer pH 4.6, 5 mM dithiothreitol) and suspended over 1 mL of well solution, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Aug 19, 2008
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.818→43.186 Å / Num. all: 5135 / Num. obs: 4894 / % possible obs: 95.3 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 7.3 % / Biso Wilson estimate: 69.16 Å2 / Rmerge(I) obs: 0.082 / Net I/σ(I): 20.3

-
Processing

Software
NameVersionClassification
BUSTER2.11.2refinement
globalphasing autoprocdata reduction
globalphasing autoprocdata scaling
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB ENTRY 4NCE

4nce


Resolution: 2.82→41.05 Å / Cor.coef. Fo:Fc: 0.9393 / Cor.coef. Fo:Fc free: 0.9319 / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.1911 233 4.78 %RANDOM
Rwork0.1696 ---
all0.1706 5135 --
obs0.1706 4872 95.03 %-
Displacement parametersBiso mean: 54.59 Å2
Baniso -1Baniso -2Baniso -3
1--4.3265 Å20 Å20 Å2
2---4.3265 Å20 Å2
3---8.653 Å2
Refine analyzeLuzzati coordinate error obs: 0.277 Å
Refinement stepCycle: LAST / Resolution: 2.82→41.05 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1287 0 25 27 1339
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.011334HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.081791HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d494SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes31HARMONIC2
X-RAY DIFFRACTIONt_gen_planes195HARMONIC5
X-RAY DIFFRACTIONt_it1334HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion3.94
X-RAY DIFFRACTIONt_other_torsion16.24
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion172SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact1543SEMIHARMONIC4
LS refinement shellResolution: 2.82→3.15 Å / Total num. of bins used: 5
RfactorNum. reflection% reflection
Rfree0.2558 69 4.79 %
Rwork0.1675 1373 -
all0.1717 1442 -
obs--95.03 %

+
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://pdbjlvh1.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