[English] 日本語
Yorodumi
- PDB-4kb7: HCV NS5B GT1B N316Y with CMPD 32 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4kb7
TitleHCV NS5B GT1B N316Y with CMPD 32
ComponentsHCV Polymerase
KeywordsREPLICATION/REPLICATION INHIBITOR / HCV Polymerase / HCV NS5B / Site IV Inhibitor / boron / P66 / P70 / RNA directed RNA Polymerase / tar7360 / RNA-dependent RNA polymerase / REPLICATION-REPLICATION 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 / 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 / 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 / induction by virus 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 / virus-mediated perturbation of host defense response / 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, 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 NS2, C-terminal domain / 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, 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 NS2, C-terminal domain / 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 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 zinc finger domain / Hepatitis C virus non-structural 5a domain 1b / Hepatitis C virus, Non-structural protein NS2 / : / NS3 RNA helicase, C-terminal helical domain / Hepacivirus nonstructural protein 2 (NS2) protease domain profile. / Hepatitis C virus non-structural 5a protein membrane anchor / 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 / Hepacivirus/Pegivirus NS3 protease domain profile. / Hepatitis C virus NS3 protease / 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-690 / Genome polyprotein
Similarity search - Component
Biological speciesHepatitis C virus
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.85 Å
AuthorsWilliams, S.P. / Kahler, K.M. / Shotwell, J.B.
CitationJournal: J.Med.Chem. / Year: 2014
Title: Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase.
Authors: Maynard, A. / Crosby, R.M. / Ellis, B. / Hamatake, R. / Hong, Z. / Johns, B.A. / Kahler, K.M. / Koble, C. / Leivers, A. / Leivers, M.R. / Mathis, A. / Peat, A.J. / Pouliot, J.J. / Roberts, C. ...Authors: Maynard, A. / Crosby, R.M. / Ellis, B. / Hamatake, R. / Hong, Z. / Johns, B.A. / Kahler, K.M. / Koble, C. / Leivers, A. / Leivers, M.R. / Mathis, A. / Peat, A.J. / Pouliot, J.J. / Roberts, C.D. / Samano, V. / Schmidt, R.M. / Smith, G.K. / Spaltenstein, A. / Stewart, E.L. / Thommes, P. / Turner, E.M. / Voitenleitner, C. / Walker, J.T. / Waitt, G. / Weatherhead, J. / Weaver, K. / Williams, S. / Wright, L. / Xiong, Z.Z. / Haigh, D. / Shotwell, J.B.
History
DepositionApr 23, 2013Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 8, 2013Provider: repository / Type: Initial release
Revision 1.1May 15, 2013Group: Other
Revision 1.2May 29, 2013Group: Database references
Revision 1.3Mar 26, 2014Group: Database references
Revision 1.4Feb 28, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / 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
Revision 1.5Mar 13, 2024Group: Source and taxonomy / Structure summary / Category: entity / pdbx_entity_src_syn / Item: _entity.details

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: HCV Polymerase
B: HCV Polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)130,4954
Polymers129,3702
Non-polymers1,1252
Water14,772820
1
A: HCV Polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,2482
Polymers64,6851
Non-polymers5621
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: HCV Polymerase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)65,2482
Polymers64,6851
Non-polymers5621
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)86.031, 106.616, 126.515
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 64685.145 Da / Num. of mol.: 2 / Fragment: HCV Polymerase 1-572 / Mutation: L47Q, F101Y, K114R, N316Y
Source method: isolated from a genetically manipulated source
Details: C-terminal 6xHis tag / Source: (gene. exp.) Hepatitis C virus / Strain: genotype 1B / Gene: NS5B / Plasmid: pET21 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P26663, RNA-directed RNA polymerase
#2: Chemical ChemComp-690 / 5-cyclopropyl-2-(4-fluorophenyl)-6-[{2-[(3R)-1-hydroxy-1,3-dihydro-2,1-benzoxaborol-3-yl]ethyl}(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide


Mass: 562.417 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H28BFN2O6S / Details: chemically synthesized
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 820 / 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: 2.24 Å3/Da / Density % sol: 45.15 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5
Details: 0.1M citrate pH5.0, 17% PEG4000, 10% glycerol, vapor diffusion, hanging drop, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.54 Å
DetectorType: RIGAKU SATURN 944 / Detector: CCD / Date: Jan 1, 2010 / Details: multi-layer mirrors
RadiationMonochromator: multi-layer mirror / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 1.811→126.515 Å / Num. all: 95243 / Num. obs: 95243 / % possible obs: 89.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 0 / Redundancy: 6.2 % / Rmerge(I) obs: 0.069 / Rsym value: 0.069 / Net I/σ(I): 15.9
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allRsym value% possible all
1.811-1.912.70.4481.82166280250.44852.6
1.91-2.023.90.2972.743034111450.29777.1
2.02-2.165.80.223.677522133300.2297.5
2.16-2.3470.1714.690062127770.171100
2.34-2.567.20.1236.384382117750.123100
2.56-2.867.20.0878.876957106980.087100
2.86-3.317.20.05812.86870394950.058100
3.31-4.057.10.0416.95751480550.0499.9
4.05-5.737.10.03617.54502463140.036100
5.73-126.5156.80.03119.52456736290.03199.8

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
SCALA3.3.16data scaling
MOLREPphasing
REFMACrefinement
PDB_EXTRACT3.11data extraction
JDirectordata collection
MOSFLMdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.85→81.53 Å / Cor.coef. Fo:Fc: 0.944 / Cor.coef. Fo:Fc free: 0.871 / WRfactor Rfree: 0.2117 / WRfactor Rwork: 0.1834 / Occupancy max: 1 / Occupancy min: 0.4 / FOM work R set: 0.8101 / SU B: 7.358 / SU ML: 0.099 / SU R Cruickshank DPI: 0.1742 / SU Rfree: 0.1524 / Isotropic thermal model: Isotropic / Cross valid method: THROUGHOUT / σ(F): 0 / σ(I): 0 / ESU R: 0.174 / ESU R Free: 0.152 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : RESIDUAL ONLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2412 4626 5 %RANDOM
Rwork0.2085 ---
all0.2101 95243 --
obs0.2101 92221 92.43 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso max: 80.3 Å2 / Biso mean: 18.733 Å2 / Biso min: 2.49 Å2
Baniso -1Baniso -2Baniso -3
1--0.54 Å20 Å20 Å2
2--1.11 Å20 Å2
3----0.57 Å2
Refinement stepCycle: LAST / Resolution: 1.85→81.53 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8362 0 80 820 9262
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0050.0228762
X-RAY DIFFRACTIONr_bond_other_d0.0010.025844
X-RAY DIFFRACTIONr_angle_refined_deg1.0171.97211962
X-RAY DIFFRACTIONr_angle_other_deg0.957314264
X-RAY DIFFRACTIONr_dihedral_angle_1_deg4.78951128
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.46723.032343
X-RAY DIFFRACTIONr_dihedral_angle_3_deg10.19151420
X-RAY DIFFRACTIONr_dihedral_angle_4_deg11.7221561
X-RAY DIFFRACTIONr_chiral_restr0.0510.21367
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.0219782
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021799
X-RAY DIFFRACTIONr_mcbond_it0.2711.55537
X-RAY DIFFRACTIONr_mcbond_other0.0381.52218
X-RAY DIFFRACTIONr_mcangle_it0.52328942
X-RAY DIFFRACTIONr_scbond_it0.73933225
X-RAY DIFFRACTIONr_scangle_it1.2434.53000
LS refinement shellResolution: 1.85→1.898 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.351 203 -
Rwork0.329 3892 -
all-4095 -
obs--56.27 %
Refinement TLS params.

T11: 0.0255 Å2 / Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.3259-0.07240.24320.1719-0.17210.83970.0381-0.06610.01950.0088-0.0308-0.01480.0336-0.0083-0.0073-0.012-0.0020.0538-0.00710.041111.31745.76347.059
20.44910.0770.24890.15870.17690.91950.03980.1056-0.0109-0.0142-0.00690.01130.04470.0697-0.03290.0201-0.0080.0565-0.00020.0497-11.56745.832-7.524
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A1 - 563
2X-RAY DIFFRACTION1A601
3X-RAY DIFFRACTION2B1 - 562
4X-RAY DIFFRACTION2B601

+
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