[English] 日本語
Yorodumi
- PDB-4eo6: HCV NS5B polymerase inhibitors: Tri-substituted acylhydrazines as... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4eo6
TitleHCV NS5B polymerase inhibitors: Tri-substituted acylhydrazines as tertiary amide bioisosteres
ComponentsRNA-directed RNA polymeraseRNA-dependent RNA polymerase
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / HCV / NS5B / RNA / RNA polymerase / polymerase inhibitor / Thumb Site 2 inhibitor / RNA-Dependent RNA Polymerase / TRANSFERASE-TRANSFERASE INHIBITOR complex
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 / : ...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 / clathrin-dependent endocytosis of virus by host cell / viral nucleocapsid / Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases / RNA helicase activity / host cell endoplasmic reticulum membrane / host cell perinuclear region of cytoplasm / RNA helicase / induction by virus of host autophagy / ribonucleoprotein complex / RNA-directed RNA polymerase / 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 / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / 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 non-structural protein NS4b ...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 / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Alpha-Beta Plaits / 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-0S2 / Genome polyprotein
Similarity search - Component
Biological speciesHepatitis C virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.791 Å
AuthorsAppleby, T.C. / Canales, E. / Watkins, W.J.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2012
Title: Tri-substituted acylhydrazines as tertiary amide bioisosteres: HCV NS5B polymerase inhibitors.
Authors: Canales, E. / Carlson, J.S. / Appleby, T. / Fenaux, M. / Lee, J. / Tian, Y. / Tirunagari, N. / Wong, M. / Watkins, W.J.
History
DepositionApr 13, 2012Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 27, 2012Provider: repository / Type: Initial release
Revision 1.1Sep 13, 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: RNA-directed RNA polymerase
B: RNA-directed RNA polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)129,0684
Polymers128,2892
Non-polymers7792
Water20,3031127
1
A: RNA-directed RNA polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,5342
Polymers64,1451
Non-polymers3901
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: RNA-directed RNA polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)64,5342
Polymers64,1451
Non-polymers3901
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)85.833, 105.714, 127.016
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein RNA-directed RNA polymerase / RNA-dependent RNA polymerase / NS5B / p68


Mass: 64144.520 Da / Num. of mol.: 2 / Fragment: UNP residues 2422-2989 / Mutation: T329V, V338A, R544Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hepatitis C virus (isolate BK) / Strain: BK / Gene: NS5B / Production host: Escherichia coli (E. coli) / References: UniProt: P26663, RNA-directed RNA polymerase
#2: Chemical ChemComp-0S2 / 5-(3,3-dimethylbut-1-yn-1-yl)-3-{[(trans-4-methylcyclohexyl)carbonyl](propan-2-yl)amino}thiophene-2-carboxylic acid


Mass: 389.551 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C22H31NO3S
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 1127 / 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: 2.25 Å3/Da / Density % sol: 45.23 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 15-20% PEG 4000, 10 % glycerol, 100 mM sodium acetate, pH 4.8-5.0, VAPOR DIFFUSION, SITTING DROP, temperature 293K
PH range: 4.8-5.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 0.9773 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Oct 7, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9773 Å / Relative weight: 1
ReflectionResolution: 1.791→48.8 Å / Num. all: 102794 / Num. obs: 102794 / % possible obs: 94.26 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 5 % / Rsym value: 0.085 / Net I/σ(I): 18

-
Processing

Software
NameVersionClassification
BOSdata collection
PHASERphasing
PHENIX(phenix.refine: 1.7_650)refinement
HKL-2000data reduction
SCALEPACKdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1C2P

1c2p


Resolution: 1.791→48.8 Å / SU ML: 0.2 / σ(F): 0 / Phase error: 23.42 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2212 1918 1.87 %
Rwork0.1801 --
obs0.1808 102794 94.26 %
Solvent computationShrinkage radii: 0.83 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 41.095 Å2 / ksol: 0.368 e/Å3
Displacement parameters
Baniso -1Baniso -2Baniso -3
1-1.6932 Å20 Å2-0 Å2
2--2.3938 Å20 Å2
3----4.087 Å2
Refinement stepCycle: LAST / Resolution: 1.791→48.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8696 0 54 1127 9877
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0068946
X-RAY DIFFRACTIONf_angle_d0.99412145
X-RAY DIFFRACTIONf_dihedral_angle_d11.9333275
X-RAY DIFFRACTIONf_chiral_restr0.0671370
X-RAY DIFFRACTIONf_plane_restr0.0051541
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.791-1.83580.2681080.2275611X-RAY DIFFRACTION75
1.8358-1.88540.23221300.20796684X-RAY DIFFRACTION88
1.8854-1.94090.25181320.18896909X-RAY DIFFRACTION91
1.9409-2.00350.29421320.18427085X-RAY DIFFRACTION93
2.0035-2.07510.20511340.1817148X-RAY DIFFRACTION95
2.0751-2.15820.23131390.17677297X-RAY DIFFRACTION96
2.1582-2.25640.21511420.17927330X-RAY DIFFRACTION97
2.2564-2.37540.24331340.18497363X-RAY DIFFRACTION97
2.3754-2.52420.24481420.18937422X-RAY DIFFRACTION97
2.5242-2.71910.23211440.19057463X-RAY DIFFRACTION98
2.7191-2.99270.23951430.18237527X-RAY DIFFRACTION98
2.9927-3.42570.18361450.17777589X-RAY DIFFRACTION98
3.4257-4.31560.2211440.15487645X-RAY DIFFRACTION98
4.3156-48.81820.18431490.18197803X-RAY DIFFRACTION97

+
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