[English] 日本語
Yorodumi
- PDB-4mia: Hepatitis C Virus polymerase NS5B genotype 1b (BK) in complex wit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4mia
TitleHepatitis C Virus polymerase NS5B genotype 1b (BK) in complex with RG7109 (N-{4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-2,5-dihydropyridin-3-yl)quinolin-3-yl]phenyl}methanesulfonamide)
ComponentsRNA-directed RNA polymerase
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / 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 / symbiont-mediated transformation of host cell / 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 / symbiont-mediated transformation of host cell / 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 / monoatomic ion transmembrane transport / 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 / RNA helicase / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont-mediated activation of host autophagy / ribonucleoprotein complex / RNA-directed RNA polymerase / viral RNA genome replication / cysteine-type endopeptidase activity / serine-type endopeptidase activity / RNA-dependent RNA polymerase activity / : / fusion of virus membrane with host endosome membrane / viral envelope / host cell nucleus / virion attachment to host cell / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / 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. / 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-28L / Genome polyprotein
Similarity search - Component
Biological speciesHepatitis C virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.8 Å
AuthorsHarris, S.F. / Villasenor, A.G.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Discovery of N-[4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a potent inhibitor of the hepatitis C virus NS5B polymerase.
Authors: Talamas, F.X. / Abbot, S.C. / Anand, S. / Brameld, K.A. / Carter, D.S. / Chen, J. / Davis, D. / de Vicente, J. / Fung, A.D. / Gong, L. / Harris, S.F. / Inbar, P. / Labadie, S.S. / Lee, E.K. ...Authors: Talamas, F.X. / Abbot, S.C. / Anand, S. / Brameld, K.A. / Carter, D.S. / Chen, J. / Davis, D. / de Vicente, J. / Fung, A.D. / Gong, L. / Harris, S.F. / Inbar, P. / Labadie, S.S. / Lee, E.K. / Lemoine, R. / Le Pogam, S. / Leveque, V. / Li, J. / McIntosh, J. / Najera, I. / Park, J. / Railkar, A. / Rajyaguru, S. / Sangi, M. / Schoenfeld, R.C. / Staben, L.R. / Tan, Y. / Taygerly, J.P. / Villasenor, A.G. / Weller, P.E.
History
DepositionAug 30, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 7, 2014Provider: repository / Type: Initial release
Revision 1.1Oct 16, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / 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)127,8556
Polymers126,7092
Non-polymers1,1464
Water4,143230
1
A: RNA-directed RNA polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,9283
Polymers63,3551
Non-polymers5732
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: RNA-directed RNA polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,9283
Polymers63,3551
Non-polymers5732
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)84.981, 104.816, 125.284
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 63354.719 Da / Num. of mol.: 2 / Fragment: UNP RESIDUES 2421-2989
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hepatitis C virus / Strain: 1b BK / Gene: NS5B / Production host: Escherichia coli (E. coli) / References: UniProt: P26663, RNA-directed RNA polymerase
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Zn
#3: Chemical ChemComp-28L / N-{4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-2,5-dihydropyridin-3-yl)quinolin-3-yl]phenyl}methanesulfonamide


Mass: 507.601 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H29N3O5S
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 230 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.2 Å3/Da / Density % sol: 44.14 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 4.64
Details: 24% peg 4000, 7.5% glycerol, 50 mM sodium citrate pH 4.64, VAPOR DIFFUSION, SITTING DROP, temperature 292K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL7-1
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: Jan 14, 2010
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 2.8→50 Å / Num. obs: 28541 / % possible obs: 99.7 % / Redundancy: 6.7 % / Biso Wilson estimate: 63.07 Å2 / Rmerge(I) obs: 0.186 / Χ2: 1.038 / Net I/σ(I): 4.3
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
2.8-2.95.60.94427650.982199
2.9-3.026.50.79328141.02199.5
3.02-3.156.80.65528151.055199.5
3.15-3.326.90.4828121.055199.8
3.32-3.5370.30728191.055199.9
3.53-3.870.20928331.0451100
3.8-4.1870.14428451.0261100
4.18-4.7970.10928911.0181100
4.79-6.036.90.12629031.0791100
6.03-506.50.05930441.032199.5

-
Processing

Software
NameVersionClassificationNB
SCALEPACKdata scaling
BUSTER-TNTBUSTER 2.11.4refinement
PDB_EXTRACT3.11data extraction
HKL-3000data reduction
BUSTER2.11.4refinement
RefinementMethod to determine structure: FOURIER SYNTHESIS / Resolution: 2.8→38.8 Å / Cor.coef. Fo:Fc: 0.9277 / Cor.coef. Fo:Fc free: 0.8792 / Occupancy max: 1 / Occupancy min: 0.5 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2788 1432 5.09 %RANDOM
Rwork0.2021 ---
obs0.206 28155 99.75 %-
Displacement parametersBiso max: 210.42 Å2 / Biso mean: 48.4331 Å2 / Biso min: 10.81 Å2
Baniso -1Baniso -2Baniso -3
1--0.2999 Å20 Å20 Å2
2---5.3493 Å20 Å2
3---5.6491 Å2
Refine analyzeLuzzati coordinate error obs: 0.318 Å
Refinement stepCycle: LAST / Resolution: 2.8→38.8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8508 0 74 230 8812
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d3063SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes170HARMONIC2
X-RAY DIFFRACTIONt_gen_planes1373HARMONIC5
X-RAY DIFFRACTIONt_it8866HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_chiral_improper_torsion1166SEMIHARMONIC5
X-RAY DIFFRACTIONt_ideal_dist_contact10836SEMIHARMONIC4
X-RAY DIFFRACTIONo_bond_d8866HARMONIC20.009
X-RAY DIFFRACTIONo_angle_deg12055HARMONIC21.05
X-RAY DIFFRACTIONt_omega_torsion2.6
X-RAY DIFFRACTIONt_other_torsion18.44
LS refinement shellResolution: 2.8→2.91 Å / Total num. of bins used: 14
RfactorNum. reflection% reflection
Rfree0.2882 144 4.97 %
Rwork0.2227 2756 -
all0.226 2900 -
obs--99.75 %

+
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