[English] 日本語
Yorodumi
- PDB-4jty: Crystal structure of HCV NS5B polymerase with COMPOUND 2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4jty
TitleCrystal structure of HCV NS5B polymerase with COMPOUND 2
ComponentsGenome polyprotein
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / RNA-DIRECTED RNA POLYMERASE / TRANSFERASE / TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX
Function / homology
Function and homology information


hepacivirin / host cell mitochondrial membrane / host cell lipid droplet / symbiont-mediated transformation of host cell / symbiont-mediated suppression of host TRAF-mediated signal transduction / symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / SH3 domain binding / nucleoside-triphosphate phosphatase ...hepacivirin / host cell mitochondrial membrane / host cell lipid droplet / symbiont-mediated transformation of host cell / symbiont-mediated suppression of host TRAF-mediated signal transduction / symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / SH3 domain binding / nucleoside-triphosphate phosphatase / channel activity / viral nucleocapsid / monoatomic ion transmembrane transport / clathrin-dependent endocytosis of virus by host cell / molecular adaptor activity / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / RNA helicase 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 / ribonucleoprotein complex / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / serine-type endopeptidase activity / cysteine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane
Similarity search - Function
Hepatitus C virus, Non-structural 5a protein, C-terminal / Hepatitis C virus NS5A, 1B domain superfamily / Hepatitis C virus non-structural protein NS2, C-terminal domain / Hepatitis C virus non-structural protein NS2, N-terminal domain / Hepatitis C virus non-structural protein NS2 / HCV NS5a protein C-terminal region / Hepatitis C virus, Non-structural protein NS4b / Hepatitis C virus, Core protein, N-terminal / Hepatitis C virus core protein, chain A superfamily / : ...Hepatitus C virus, Non-structural 5a protein, C-terminal / Hepatitis C virus NS5A, 1B domain superfamily / Hepatitis C virus non-structural protein NS2, C-terminal domain / Hepatitis C virus non-structural protein NS2, N-terminal domain / Hepatitis C virus non-structural protein NS2 / HCV NS5a protein C-terminal region / Hepatitis C virus, Non-structural protein NS4b / Hepatitis C virus, Core protein, N-terminal / Hepatitis C virus core protein, chain A superfamily / : / Hepatitis C virus non-structural protein NS4b / Hepatitis C virus capsid protein / Hepatitis C virus, Non-structural protein NS2 / Hepatitis C virus, Non-structural 5a protein / Hepatitis C virus, Non-structural 5a protein, domain 1a / Hepatitis C virus non-structural 5a, 1B domain / NS5A domain 1a superfamily / : / Hepatitis C virus non-structural 5a protein membrane anchor / Hepatitis C virus non-structural 5a zinc finger domain / Hepatitis C virus non-structural 5a domain 1b / NS3 RNA helicase, C-terminal helical domain / Hepacivirus nonstructural protein 2 (NS2) protease domain profile. / Hepatitis C virus, Non-structural protein NS4a / Hepatitis C virus non-structural protein NS4a / Hepatitis C virus, Core protein, C-terminal / Hepatitis C virus core protein / Hepatitis C virus, Non-structural protein E2/NS1 / Hepatitis C virus non-structural protein E2/NS1 / Hepatitis C virus, Envelope glycoprotein E1 / Hepatitis C virus envelope glycoprotein E1 / RNA dependent RNA polymerase, hepatitis C virus / Viral RNA dependent RNA polymerase / Hepatitis C virus, NS3 protease, Peptidase S29 / Hepatitis C virus NS3 protease / Hepacivirus/Pegivirus NS3 protease domain profile. / DEAD box, Flavivirus / Flavivirus DEAD domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / Reverse transcriptase/Diguanylate cyclase domain / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Peptidase S1, PA clan, chymotrypsin-like fold / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Chem-1NV / Genome polyprotein
Similarity search - Component
Biological speciesHepatitis C virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.6 Å
AuthorsCoulombe, R.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Molecular Dynamics Simulations and Structure-Based Rational Design Lead to Allosteric HCV NS5B Polymerase Thumb Pocket 2 Inhibitor with Picomolar Cellular Replicon Potency.
Authors: Hucke, O. / Coulombe, R. / Bonneau, P. / Bertrand-Laperle, M. / Brochu, C. / Gillard, J. / Joly, M.A. / Landry, S. / Lepage, O. / Llinas-Brunet, M. / Pesant, M. / Poirier, M. / Poirier, M. / ...Authors: Hucke, O. / Coulombe, R. / Bonneau, P. / Bertrand-Laperle, M. / Brochu, C. / Gillard, J. / Joly, M.A. / Landry, S. / Lepage, O. / Llinas-Brunet, M. / Pesant, M. / Poirier, M. / Poirier, M. / McKercher, G. / Marquis, M. / Kukolj, G. / Beaulieu, P.L. / Stammers, T.A.
History
DepositionMar 24, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 3, 2013Provider: repository / Type: Initial release
Revision 1.1Mar 26, 2014Group: Database references
Revision 1.2Sep 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_conn / 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_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_asym_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _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: Genome polyprotein
B: Genome polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)129,7918
Polymers128,5712
Non-polymers1,2206
Water7,873437
1
A: Genome polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,8954
Polymers64,2861
Non-polymers6103
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Genome polyprotein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,8954
Polymers64,2861
Non-polymers6103
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)106.200, 107.570, 134.520
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Genome polyprotein / Core protein p21 / Capsid protein C / p21 / Core protein p19 / Envelope glycoprotein E1 / gp32 / ...Core protein p21 / Capsid protein C / p21 / Core protein p19 / Envelope glycoprotein E1 / gp32 / gp35 / Envelope glycoprotein E2 / NS1 / gp68 / gp70 / p7 / Protease NS2-3 / p23 / Serine protease NS3 / Hepacivirin / NS3P / p70 / Non-structural protein 4A / NS4A / p8 / Non-structural protein 4B / NS4B / p27 / Non-structural protein 5A / NS5A / p56 / RNA-directed RNA polymerase / NS5B / p68


Mass: 64285.637 Da / Num. of mol.: 2
Fragment: RNA-DIRECTED RNA POLYMERASE, UNP RESIDUES 2420-2989
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hepatitis C virus / Strain: 1BJ4 / Gene: NS5B / Plasmid: PET29B / Production host: Escherichia coli (E. coli) / Strain (production host): JM109(DE3)
References: UniProt: O92972, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases, hepacivirin, nucleoside-triphosphate phosphatase, RNA helicase, RNA-directed RNA polymerase
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-1NV / 3-{[4-oxo-1-(2,4,6-trifluorobenzyl)-1,4-dihydroquinazolin-6-yl]oxy}-2-(trifluoromethyl)benzamide


Mass: 493.358 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H13F6N3O3
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 437 / 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: 2.99 Å3/Da / Density % sol: 58.84 %
Crystal growTemperature: 284 K / Method: vapor diffusion, hanging drop / pH: 5.4
Details: 100 mM MES, 21% PEGmme 5000, 400 mM Ammonium sulfate, 10% glycerol, pH 5.4, VAPOR DIFFUSION, HANGING DROP, temperature 284K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jun 5, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.59→50 Å / Num. obs: 48180 / % possible obs: 98.9 % / Redundancy: 6.64 % / Rmerge(I) obs: 0.096 / Net I/σ(I): 17.53
Reflection shellResolution: 2.59→2.74 Å / Redundancy: 6.61 % / Rmerge(I) obs: 0.433 / Mean I/σ(I) obs: 3.05 / Num. unique all: 7229 / % possible all: 93.4

-
Processing

Software
NameVersionClassification
HKL-2000data collection
CNX2002refinement
XDSdata reduction
XDSdata scaling
CNX2002phasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3MWV

3mwv


Resolution: 2.6→50 Å / σ(F): 1 / Stereochemistry target values: Engh & Huber
RfactorNum. reflectionSelection details
Rfree0.25 3118 RANDOM
Rwork0.197 --
obs-48036 -
Refinement stepCycle: LAST / Resolution: 2.6→50 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8724 0 84 437 9245
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.006052
X-RAY DIFFRACTIONc_angle_deg1.24712

+
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