[English] 日本語
Yorodumi
- PDB-3rc6: Molecular mechanisms of viral and host-cell substrate recognition... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3rc6
TitleMolecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease
ComponentsNS3/4A
KeywordsVIRAL PROTEIN / HYDROLASE / drug resistance / drug design / Protease inhibitors / serine protease
Function / homology
Function and homology information


host cell mitochondrial membrane / host cell lipid droplet / transformation of host cell by virus / modulation by virus of host G1/S transition checkpoint / suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity / lipid droplet / suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / host cell endoplasmic reticulum membrane / pore formation by virus in membrane of host cell / protein complex oligomerization ...host cell mitochondrial membrane / host cell lipid droplet / transformation of host cell by virus / modulation by virus of host G1/S transition checkpoint / suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity / lipid droplet / suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity / host cell endoplasmic reticulum membrane / pore formation by virus in membrane of host cell / protein complex oligomerization / suppression by virus of host TRAF-mediated signal transduction => GO:0039527 / ion channel activity / clathrin-dependent endocytosis of virus by host cell / host cell perinuclear region of cytoplasm / viral nucleocapsid / RNA helicase activity / integral to membrane of host cell / induction by virus of host autophagy / cysteine-type endopeptidase activity / viral RNA genome replication / virion attachment to host cell / RNA-directed 5'-3' RNA polymerase activity / suppression by virus of host type I interferon-mediated signaling pathway / fusion of virus membrane with host endosome membrane / viral envelope / serine-type endopeptidase activity / host cell nucleus / structural molecule activity / host cell plasma membrane / virion membrane / ATP hydrolysis activity / RNA binding / zinc ion binding / integral component of membrane / ATP binding / plasma membrane / cytoplasm
Similarity search - Function
Thrombin, subunit H - #120 / Hepatitis C virus core protein, chain A superfamily / HCV NS5a protein C-terminal region / 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 NS4b / Hepatitis C virus, Non-structural protein NS4b / Hepatitis C virus capsid protein ...Thrombin, subunit H - #120 / Hepatitis C virus core protein, chain A superfamily / HCV NS5a protein C-terminal region / 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 NS4b / Hepatitis C virus, Non-structural protein NS4b / Hepatitis C virus capsid protein / Hepatitis C virus, Core protein, N-terminal / Hepatitis C virus non-structural 5a, 1B domain / NS5A domain 1a superfamily / Hepatitis C virus non-structural protein NS2 / Hepatitis C virus non-structural 5a protein membrane anchor / Hepatitis C virus, Non-structural 5a protein / Hepatitis C virus, Non-structural protein NS2 / 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 5a protein, domain 1a / 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 / Viral RNA dependent RNA polymerase / RNA dependent RNA polymerase, hepatitis C virus / Hepatitis C virus, NS3 protease, Peptidase S29 / Hepatitis C virus NS3 protease / Hepacivirus/Pegivirus NS3 protease domain profile. / Flavivirus DEAD domain / DEAD box, Flavivirus / helicase superfamily c-terminal domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / Helicase, C-terminal / DEAD-like helicases superfamily / Helicase superfamily 1/2, ATP-binding domain / Trypsin-like serine proteases / Thrombin, subunit H / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / Reverse transcriptase/Diguanylate cyclase domain / Peptidase S1, PA clan, chymotrypsin-like fold / DNA/RNA polymerase superfamily / Peptidase S1, PA clan / Beta Barrel / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta
Similarity search - Domain/homology
Biological speciesHepatitis C virus subtype 1a
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.3 Å
AuthorsSchiffer, C.A. / Romano, K.P.
CitationJournal: J.Virol. / Year: 2011
Title: Molecular mechanisms of viral and host-cell substrate recognition by HCV NS3/4A protease.
Authors: Romano, K.P. / Laine, J.M. / Deveau, L.M. / Cao, H. / Massi, F. / Schiffer, C.A.
History
DepositionMar 30, 2011Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 4, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Aug 10, 2011Group: Database references
Revision 1.3Aug 23, 2017Group: Refinement description / Source and taxonomy / Category: entity_src_gen / software
Revision 1.4Nov 8, 2017Group: Refinement description / Category: software
Item: _software.classification / _software.contact_author ..._software.classification / _software.contact_author / _software.contact_author_email / _software.date / _software.language / _software.location / _software.name / _software.type / _software.version

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: NS3/4A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)21,5532
Polymers21,4871
Non-polymers651
Water2,990166
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)54.850, 58.581, 60.901
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein NS3/4A


Mass: 21487.330 Da / Num. of mol.: 1
Fragment: NS4A (UNP residues 1678-1688), NS3 (UNP residues 1027-1208)
Mutation: A1027S, P1028G, I1029D, L1039E, L1040E, I1043Q, I1044E, L1047Q, A1066T, C1073S, C1078L, I1098T, P1112Q, S1165A, C1185S, C1679S, V1686I, I1687N
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hepatitis C virus subtype 1a / Gene: NS3 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: A8DG50
#2: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 166 / Source method: isolated from a natural source / Formula: H2O
Sequence detailsTHE COFACTOR 4A RESIDUES 990-1000 (GLY SER VAL VAL ILE VAL GLY ARG ILE ASN LEU) IN THIS ENTRY ...THE COFACTOR 4A RESIDUES 990-1000 (GLY SER VAL VAL ILE VAL GLY ARG ILE ASN LEU) IN THIS ENTRY CORRESPOND TO RESIDUES NUMBERING 1678-1688 OF DATABASE SEQUENCE REFERENCE (UNP A8DG50). THIS PEPTIDE IS COVALENTLY LINKED TO THE N-TERMINUS OF NS3. C1679S MUTATION WAS ENGINEERED TO PREVENT DISULFIDE FORMATION. THE V1686I AND I1687N WERE ENGINEERED TO OPTIMIZE THE LINKER BETWEEN THE COFACTOR 4A AND NS3.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.29 Å3/Da / Density % sol: 46.22 %
Crystal growTemperature: 295 K / Method: hanging drop, vapor diffusion / pH: 6.2
Details: 20-25% PEG 3350, 0.1M MES (pH 6.5), 4% ammonium sulfate, hanging drop, vapor diffusion, temperature 295K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F
DetectorDate: Jul 21, 2010
RadiationProtocol: SINGLE WAVELENGTH / Scattering type: x-ray
Radiation wavelengthRelative weight: 1
ReflectionResolution: 1.3→50 Å / Num. obs: 45595 / % possible obs: 93.1 % / Redundancy: 4.2 % / Rmerge(I) obs: 0.048 / Χ2: 1.004 / Net I/σ(I): 14.8
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
1.3-1.3540.37746791.001197.1
1.35-1.44.10.28646471.006196.6
1.4-1.464.10.21446591.007196.1
1.46-1.544.20.15346300.999195.5
1.54-1.644.20.11246031.006195.2
1.64-1.764.30.08445871.003194.2
1.76-1.944.30.06945441.003193.1
1.94-2.224.10.06344961.004191.3
2.22-2.84.10.05244691.008190
2.8-504.30.03242811.005182.8

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
REFMACrefinement
PDB_EXTRACT3.1data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 3M5M
Resolution: 1.3→26.62 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.958 / WRfactor Rfree: 0.2099 / WRfactor Rwork: 0.1794 / Occupancy max: 1 / Occupancy min: 0.25 / FOM work R set: 0.8976 / SU B: 1.419 / SU ML: 0.028 / SU R Cruickshank DPI: 0.0533 / SU Rfree: 0.051 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.051 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: RESIDUAL ONLY
RfactorNum. reflection% reflectionSelection details
Rfree0.191 2301 5.1 %RANDOM
Rwork0.1608 ---
obs0.1623 45433 92.69 %-
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 max: 62.72 Å2 / Biso mean: 11.9581 Å2 / Biso min: 3.15 Å2
Baniso -1Baniso -2Baniso -3
1--0.09 Å20 Å20 Å2
2---0.88 Å20 Å2
3---0.97 Å2
Refinement stepCycle: LAST / Resolution: 1.3→26.62 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1465 0 1 166 1632
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0090.0211531
X-RAY DIFFRACTIONr_bond_other_d0.0010.021022
X-RAY DIFFRACTIONr_angle_refined_deg1.2941.9552091
X-RAY DIFFRACTIONr_angle_other_deg0.80732500
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9635213
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.14422.67956
X-RAY DIFFRACTIONr_dihedral_angle_3_deg11.37915242
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.6231513
X-RAY DIFFRACTIONr_chiral_restr0.0780.2245
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.0211749
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02306
X-RAY DIFFRACTIONr_mcbond_it1.0051.51014
X-RAY DIFFRACTIONr_mcbond_other0.2731.5422
X-RAY DIFFRACTIONr_mcangle_it1.65121634
X-RAY DIFFRACTIONr_scbond_it2.2863517
X-RAY DIFFRACTIONr_scangle_it3.3474.5451
X-RAY DIFFRACTIONr_rigid_bond_restr0.84432553
LS refinement shellResolution: 1.3→1.333 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.211 172 -
Rwork0.194 3169 -
all-3341 -
obs--93.9 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
10.6005-2.9165-3.37118.478411.656411.59550.1573-0.05850.1258-0.66480.0407-0.0602-0.95840.244-0.1980.20860.02150.04340.13320.03790.09666.2002-21.6156-2.5018
20.7032-0.3198-0.8094.46730.53231.01120.04590.02520.0187-0.02310.0008-0.1499-0.04020.0597-0.04670.07420.0014-0.00070.07340.00740.09515.2642-4.865516.1121
3-1.6534-1.904-2.184612.094-6.98868.7589-0.0417-0.45180.08230.7352-0.0806-0.5253-0.4985-0.18020.12230.1484-0.05290.04280.2079-0.11060.1249-0.3665.943128.9734
43.5297-1.054-3.30321.78580.52473.26130.0915-0.11260.14690.01360.0181-0.0775-0.06760.1967-0.10960.0931-0.00720.0030.06420.00540.1034.99394.468118.1807
53.8115-1.79180.37276.0976-0.12593.36280.11160.20860.0052-0.5102-0.1661-0.1723-0.06620.05510.05450.10690.0070.03810.0660.01520.083610.1158-5.47738.6752
613.57950.2962-9.70610.14291.653413.52560.0774-0.39170.01210.02670.0729-0.1572-0.3480.6756-0.15030.0815-0.0402-0.02360.0821-0.00130.169311.8753-2.233922.1915
71.6332-0.3307-0.78061.62260.0196.03390.14710.10980.0443-0.089-0.0017-0.04990.0095-0.2508-0.14540.07150.0066-0.00140.07980.01760.085-0.1724-4.759515.8803
81.0601-0.1161-0.27060.54970.16890.26340.0019-0.0197-0.03390.0025-0.0101-0.00740.00340.00760.00810.08050.0008-0.00170.07080.00460.0833-1.945-11.87121.5539
92.08160.9793-0.43791.072-0.17671.3389-0.0006-0.0376-0.1162-0.0446-0.0873-0.08730.05560.13060.08780.07130.00890.0090.07960.01160.108410.2189-13.295516.2357
101.39010.5577-0.03250.91560.49450.7296-0.0011-0.0436-0.11010.0257-0.0453-0.03070.03970.01190.04630.08210.0026-0.00040.06840.00830.0931-0.6166-17.929321.5944
111.6894-0.0774-1.60010.51220.09631.37170.0429-0.28650.05820.062-0.0442-0.0059-0.03620.17070.00130.0787-0.0161-0.00340.1094-0.01530.0731-4.0834-7.038334.7578
124.10451.7335-3.37211.6466-2.43295.2866-0.0202-0.09150.5717-0.1434-0.03770.32680.07470.02160.05790.08930.014-0.01820.0367-0.030.2427-8.42181.719323.6642
1313.73677.9437-7.48745.951-3.78323.57040.2030.07670.64390.02720.21630.093-0.0698-0.1749-0.41940.07620.01450.04230.0614-0.01610.1658-15.24841.465928.5889
142.8382-0.6685-1.35823.0622-0.5461.94450.01750.0056-0.0501-0.0410.04440.14080.003-0.1442-0.0620.07320.00390.00910.09850.01120.0789-20.308-9.242629.162
152.0370.03271.8623-1.4275-3.39818.08650.08630.1030.7780.0967-0.0695-0.1445-0.41420.2361-0.01680.09840.03120.08280.07710.050.2442-20.50283.190723.7366
162.6337-3.12040.39.6465-1.59570.7822-0.08050.03760.09350.05810.2476-0.0291-0.0195-0.1102-0.1670.08720.0152-0.00150.10210.04650.0785-14.71692.10815.4285
170.43680.1613-1.28250.2170.8596.2820.0772-0.06220.1432-0.0089-0.0440.1191-0.15880.0355-0.03330.08490.00070.01180.0934-0.01950.1071-8.4915-3.714628.8877
182.4673-0.7228-0.06870.28120.72612.70130.0155-0.05030.06450.0258-0.00520.0140.05310.0325-0.01030.0833-0.00360.00890.07820.00170.0862-9.7676-8.5327.8481
194.30543.37261.68352.6004-5.19758.3494-0.06290.58970.18410.04150.520.61340.2052-0.3252-0.45710.06950.0092-0.02240.19510.08090.1194-22.0678-3.608716.0334
204.2418-2.29081.10112.2512-1.18491.5127-0.0178-0.1313-0.16960.05320.05040.07430.0638-0.0076-0.03260.088-0.00580.00230.08250.01310.0799-9.7691-14.924228.956
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A980 - 989
2X-RAY DIFFRACTION2A990 - 997
3X-RAY DIFFRACTION3A998 - 1005
4X-RAY DIFFRACTION4A1006 - 1012
5X-RAY DIFFRACTION5A1013 - 1025
6X-RAY DIFFRACTION6A1026 - 1031
7X-RAY DIFFRACTION7A1032 - 1042
8X-RAY DIFFRACTION8A1043 - 1061
9X-RAY DIFFRACTION9A1062 - 1071
10X-RAY DIFFRACTION10A1072 - 1088
11X-RAY DIFFRACTION11A1089 - 1104
12X-RAY DIFFRACTION12A1105 - 1111
13X-RAY DIFFRACTION13A1112 - 1117
14X-RAY DIFFRACTION14A1118 - 1125
15X-RAY DIFFRACTION15A1126 - 1130
16X-RAY DIFFRACTION16A1131 - 1136
17X-RAY DIFFRACTION17A1137 - 1148
18X-RAY DIFFRACTION18A1149 - 1155
19X-RAY DIFFRACTION19A1156 - 1164
20X-RAY DIFFRACTION20A1165 - 1181

+
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