[English] 日本語
Yorodumi
- PDB-2wcx: Crystal Structure of Hepatitis C Virus NS5B Polymerase in Complex... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2wcx
TitleCrystal Structure of Hepatitis C Virus NS5B Polymerase in Complex with Thienopyrrole-Based Finger-Loop Inhibitors
ComponentsRNA-DIRECTED RNA POLYMERASERNA-dependent RNA polymerase
KeywordsHYDROLASE / ENVELOPE PROTEIN / HEPATITIS C VIRUS / RNA-DEPENDENT RNA-POLYMERASE / NUCLEOTIDE-BINDING / ALLOSTERIC INHIBITOR / NON NUCLEOSIDE INHIBITOR / NNI / HCV / NS5B / MEMBRANE / HELICASE / POLYMERASE / ATP-BINDING / RNA-BINDING / GENOTYPE 1B / VIRAL PROTEIN / TRANSMEMBRANE / RNA REPLICATION
Function / homology
Function and homology information


hepacivirin / host cell mitochondrial membrane / host cell lipid droplet / symbiont-mediated suppression of host TRAF-mediated signal transduction / transformation of host cell by virus / 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 suppression of host TRAF-mediated signal transduction / transformation of host cell by virus / 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 / protein complex oligomerization / monoatomic ion channel activity / viral nucleocapsid / clathrin-dependent endocytosis of virus by host cell / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / RNA helicase activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / RNA helicase / ribonucleoprotein complex / induction by virus of host autophagy / RNA-directed RNA polymerase / virus-mediated perturbation of host defense response / viral RNA genome replication / cysteine-type endopeptidase activity / RNA-dependent RNA polymerase activity / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / RNA binding / zinc ion binding / ATP binding / membrane
Similarity search - Function
: / 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 / 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 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 / 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. / Reverse transcriptase/Diguanylate cyclase domain / 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 / Alpha-Beta Plaits / 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 / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
: / Chem-VGC / Genome polyprotein
Similarity search - Component
Biological speciesHEPATITIS C VIRUS
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsDi Marco, S.
Citation
Journal: Chemmedchem / Year: 2009
Title: Optimization of Thienopyrrole-Based Finger-Loop Inhibitors of the Hepatitis C Virus Ns5B Polymerase.
Authors: Martin Hernando, J.I. / Ontoria, J.M. / Malancona, S. / Attenni, B. / Fiore, F. / Bonelli, F. / Koch, U. / Di Marco, S. / Colarusso, S. / Ponzi, S. / Gennari, N. / Vignetti, S.E. / Del ...Authors: Martin Hernando, J.I. / Ontoria, J.M. / Malancona, S. / Attenni, B. / Fiore, F. / Bonelli, F. / Koch, U. / Di Marco, S. / Colarusso, S. / Ponzi, S. / Gennari, N. / Vignetti, S.E. / Del Rosario Rico Ferreira, M. / Habermann, J. / Rowley, M. / Narjes, F.
#1: Journal: J.Biol.Chem. / Year: 2005
Title: Interdomain Communication in Hepatitis C Virus Polymerase Abolished by Small Molecule Inhibitors Bound to a Novel Allosteric Site.
Authors: Di Marco, S. / Volpari, C. / Tomei, L. / Altamura, S. / Harper, S. / Narjes, F. / Koch, U. / Rowley, M. / De Francesco, R. / Migliaccio, G. / Carfi, A.
History
DepositionMar 17, 2009Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 18, 2009Provider: repository / Type: Initial release
Revision 1.1Nov 23, 2011Group: Atomic model / Database references ...Atomic model / Database references / Derived calculations / Non-polymer description / Other / Refinement description / Structure summary / Version format compliance
Revision 1.2Dec 13, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _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: RNA-DIRECTED RNA POLYMERASE
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,2224
Polymers59,7731
Non-polymers4493
Water9,134507
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)68.407, 94.708, 95.540
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

-
Components

#1: Protein RNA-DIRECTED RNA POLYMERASE / RNA-dependent RNA polymerase / HEPATITIS C VIRUS RNA-DEPENDENT-RNA-POLYMERASE / NS5B / P68


Mass: 59772.711 Da / Num. of mol.: 1 / Fragment: NS5B, RESIDUES 2420-2955
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HEPATITIS C VIRUS / Strain: (ISOLATE BK) / Description: GENBANK ACCESSION NUMBER AB016785 / Variant: GENOTYPE 1B / Plasmid: PT7.7 / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P26663, RNA-directed RNA polymerase
#2: Chemical ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mn
#3: Chemical ChemComp-VGC / 6-CYCLOHEXYL-4-METHYL-5-PHENYL-4H-THIENO[3,2-B]PYRROLE-2-CARBOXYLIC ACID


Mass: 339.451 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H21NO2S
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 507 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsNS5B PROTEIN, GENOTYPE 1B AND STRAIN BK, LACKING THE C- TERMINAL 55 AMINO ACIDS. TOTAL AMINO ACIDS ...NS5B PROTEIN, GENOTYPE 1B AND STRAIN BK, LACKING THE C- TERMINAL 55 AMINO ACIDS. TOTAL AMINO ACIDS 535, UNIPROT REFERENCE P26663, 2420-2955

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.45 Å3/Da / Density % sol: 49.41 % / Description: NONE
Crystal growpH: 6 / Details: pH 6.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ESRF / Beamline: ID14-1 / Wavelength: 0.931
DetectorType: ADSC CCD / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.931 Å / Relative weight: 1
ReflectionResolution: 2→33.71 Å / Num. obs: 42683 / % possible obs: 97.2 % / Observed criterion σ(I): 2 / Redundancy: 6.9 % / Biso Wilson estimate: 21.65 Å2 / Rmerge(I) obs: 0.09 / Net I/σ(I): 18
Reflection shellResolution: 2→2.11 Å / Redundancy: 6.2 % / Rmerge(I) obs: 0.35 / Mean I/σ(I) obs: 5.2 / % possible all: 94.9

-
Processing

Software
NameVersionClassification
REFMAC5refinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1CSJ

1csj


Resolution: 2→95.35 Å / Cor.coef. Fo:Fc: 0.954 / Cor.coef. Fo:Fc free: 0.926 / SU B: 5.099 / SU ML: 0.146 / Cross valid method: THROUGHOUT / ESU R: 0.159 / ESU R Free: 0.146 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. NO ELECTRON DENSITY WAS PRESENT FOR RESIDUES 22-35, 148-152 AND 532-536 WHICH WERE THEREFORE EXCLUDED FROM THE REFINEMENT. IN ADDITION, ...Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS. NO ELECTRON DENSITY WAS PRESENT FOR RESIDUES 22-35, 148-152 AND 532-536 WHICH WERE THEREFORE EXCLUDED FROM THE REFINEMENT. IN ADDITION, SIDE CHAIN DENSITY FOR RESIDUES GLU18, LYS20 AND LEU21 WAS MISSING AND THEREFORE THESE RESIDUES HAVE BEEN MODELED AS ALANINE.
RfactorNum. reflection% reflectionSelection details
Rfree0.2092 2088 5.1 %RANDOM
Rwork0.16717 ---
obs0.16931 39241 96.83 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: BABINET MODEL WITH MASK
Displacement parametersBiso mean: 22.471 Å2
Baniso -1Baniso -2Baniso -3
1--0.08 Å20 Å20 Å2
2---0.21 Å20 Å2
3---0.3 Å2
Refinement stepCycle: LAST / Resolution: 2→95.35 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3968 0 26 507 4501
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0220.0214086
X-RAY DIFFRACTIONr_bond_other_d0.0010.023717
X-RAY DIFFRACTIONr_angle_refined_deg1.9091.9635541
X-RAY DIFFRACTIONr_angle_other_deg1.6738647
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.6393509
X-RAY DIFFRACTIONr_dihedral_angle_2_deg
X-RAY DIFFRACTIONr_dihedral_angle_3_deg18.59415753
X-RAY DIFFRACTIONr_dihedral_angle_4_deg
X-RAY DIFFRACTIONr_chiral_restr0.1250.2626
X-RAY DIFFRACTIONr_gen_planes_refined0.0090.024494
X-RAY DIFFRACTIONr_gen_planes_other0.0030.02827
X-RAY DIFFRACTIONr_nbd_refined0.2520.3998
X-RAY DIFFRACTIONr_nbd_other0.3210.33855
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other1.250.54
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.2290.5476
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2170.317
X-RAY DIFFRACTIONr_symmetry_vdw_other0.2540.334
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.8290.536
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it1.1961.52554
X-RAY DIFFRACTIONr_mcbond_other
X-RAY DIFFRACTIONr_mcangle_it2.23324126
X-RAY DIFFRACTIONr_mcangle_other
X-RAY DIFFRACTIONr_scbond_it3.50931532
X-RAY DIFFRACTIONr_scbond_other
X-RAY DIFFRACTIONr_scangle_it5.6814.51415
X-RAY DIFFRACTIONr_scangle_other
X-RAY DIFFRACTIONr_long_range_B_refined
X-RAY DIFFRACTIONr_long_range_B_other
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 2→2.052 Å / Total num. of bins used: 20 /
RfactorNum. reflection
Rfree0.247 138
Rwork0.178 2768

+
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