[English] 日本語
Yorodumi
- PDB-3p8o: Crystal structure of HCV NS3/NS4A protease complexed with des-bro... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3p8o
TitleCrystal structure of HCV NS3/NS4A protease complexed with des-bromine analogue of BI 201335
Components
  • HCV non-structural protein 4A
  • HCV serine protease NS3
KeywordsHYDROLASE/HYDROLASE inhibitor / Hepatitis C Virus / NS3 / NS4A / halogen bond / serine protease / HYDROLASE-HYDROLASE inhibitor complex
Function / homology
Function and homology information


RNA stabilization / RNA folding chaperone / DNA/DNA annealing activity / RNA strand annealing activity / 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 ...RNA stabilization / RNA folding chaperone / DNA/DNA annealing activity / RNA strand annealing activity / 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 / protein-DNA complex / 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 / DNA binding / RNA binding / zinc ion binding / ATP binding / membrane
Similarity search - Function
Thrombin, subunit H - #120 / 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 ...Thrombin, subunit H - #120 / 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 / DEAD box, Flavivirus / Flavivirus DEAD domain / helicase superfamily c-terminal domain / Trypsin-like serine proteases / 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 / Thrombin, subunit H / Reverse transcriptase/Diguanylate cyclase domain / 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 / Beta Barrel / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta
Similarity search - Domain/homology
N-[(CYCLOPENTYLOXY)CARBONYL]-3-METHYL-L-VALYL-(4R)-N-[(1R,2S)-1-CARBOXY-2-ETHENYLCYCLOPROPYL]-4-[(7-METHOXY-2-{2-[(2-METHYLPROPANOYL)AMINO]-1,3-THIAZOL-4-YL}QUINOLIN-4-YL)OXY]-L-PROLINAMIDE / Chem-L5T / Genome polyprotein
Similarity search - Component
Biological speciesHepatitis C virus
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsLemke, C.T.
CitationJournal: J.Biol.Chem. / Year: 2011
Title: Combined X-ray, NMR, and kinetic analyses reveal uncommon binding characteristics of the hepatitis C virus NS3-NS4A protease inhibitor BI 201335.
Authors: Lemke, C.T. / Goudreau, N. / Zhao, S. / Hucke, O. / Thibeault, D. / Llinas-Brunet, M. / White, P.W.
History
DepositionOct 14, 2010Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 26, 2011Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Dec 12, 2012Group: Other
Revision 1.3Nov 8, 2017Group: Advisory / Refinement description / Category: pdbx_unobs_or_zero_occ_atoms / software
Revision 1.4Nov 6, 2024Group: Advisory / Data collection ...Advisory / 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 / pdbx_struct_conn_angle / pdbx_unobs_or_zero_occ_atoms / struct_conn / 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 / _pdbx_entry_details.has_protein_modification / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr1_auth_asym_id / _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_asym_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_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: HCV serine protease NS3
B: HCV serine protease NS3
C: HCV non-structural protein 4A
D: HCV non-structural protein 4A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)44,5868
Polymers42,9584
Non-polymers1,6284
Water1,18966
1
A: HCV serine protease NS3
C: HCV non-structural protein 4A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,2934
Polymers21,4792
Non-polymers8142
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2500 Å2
ΔGint-21 kcal/mol
Surface area8880 Å2
MethodPISA
2
B: HCV serine protease NS3
D: HCV non-structural protein 4A
hetero molecules


Theoretical massNumber of molelcules
Total (without water)22,2934
Polymers21,4792
Non-polymers8142
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2590 Å2
ΔGint-21 kcal/mol
Surface area8920 Å2
MethodPISA
Unit cell
Length a, b, c (Å)94.965, 94.965, 81.800
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number169
Space group name H-MP61

-
Components

#1: Protein HCV serine protease NS3


Mass: 19663.635 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Hepatitis C virus / Strain: isolate Japanese / Gene: POLG_HCVJA / Production host: Escherichia coli (E. coli) / References: UniProt: P26662, hepacivirin
#2: Protein/peptide HCV non-structural protein 4A


Mass: 1815.277 Da / Num. of mol.: 2 / Fragment: NS3 interacting peptide / Source method: obtained synthetically / References: UniProt: P26662*PLUS
#3: Chemical ChemComp-NA / SODIUM ION


Mass: 22.990 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Na
#4: Chemical ChemComp-L5T / N-[(cyclopentyloxy)carbonyl]-3-methyl-L-valyl-(4R)-N-[(1R,2S)-1-carboxy-2-ethenylcyclopropyl]-4-[(7-methoxy-2-{2-[(2-methylpropanoyl)amino]-1,3-thiazol-4-yl}quinolin-4-yl)oxy]-L-prolinamide


Type: Peptide-like / Class: Enzyme inhibitor / Mass: 790.925 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C40H50N6O9S
References: N-[(CYCLOPENTYLOXY)CARBONYL]-3-METHYL-L-VALYL-(4R)-N-[(1R,2S)-1-CARBOXY-2-ETHENYLCYCLOPROPYL]-4-[(7-METHOXY-2-{2-[(2-METHYLPROPANOYL)AMINO]-1,3-THIAZOL-4-YL}QUINOLIN-4-YL)OXY]-L-PROLINAMIDE
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 66 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY
Sequence detailsTHESE ARE NATURAL VARIANTS ACCORDING TO UNIPROT.

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.48 Å3/Da / Density % sol: 50.38 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 3M NaCl, 0.1M Na Citrate, 2.5% T-butanol, 20mM OBG, 5mM DTT, 3mM sodium azide, pH 6.0, VAPOR DIFFUSION, HANGING DROP, temperature 291K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E SUPERBRIGHT / Wavelength: 1.5418 Å
DetectorType: MARRESEARCH / Detector: IMAGE PLATE
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.3→40 Å / Num. obs: 18452 / % possible obs: 98.6 % / Redundancy: 10.6 % / Rmerge(I) obs: 0.048 / Χ2: 1.003 / Net I/σ(I): 23.2
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique allΧ2Diffraction-ID% possible all
2.3-2.387.70.38316550.991188.6
2.38-2.4890.3218121197.8
2.48-2.5910.20.28918590.983199.9
2.59-2.7310.90.19318691.0181100
2.73-2.911.20.12418540.9981100
2.9-3.1211.30.08418570.9741100
3.12-3.4411.30.05918740.971100
3.44-3.9311.30.04218850.9861100
3.93-4.9511.20.03218701.019199.9
4.95-4011.10.03119171.082199.6

-
Processing

Software
NameVersionClassificationNB
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACT3.1data extraction
MAR345dtbdata collection
CNSphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.3→40 Å / Occupancy max: 1 / Occupancy min: 0 / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2553 872 4.7 %Random
Rwork0.2077 ---
obs-17940 95.9 %-
Displacement parametersBiso max: 97.18 Å2 / Biso mean: 48.4143 Å2 / Biso min: 26.31 Å2
Baniso -1Baniso -2Baniso -3
1-0.114 Å20.036 Å20 Å2
2--0.114 Å20 Å2
3----0.227 Å2
Refinement stepCycle: LAST / Resolution: 2.3→40 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2834 0 114 66 3014
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.009
X-RAY DIFFRACTIONc_angle_d0.982
X-RAY DIFFRACTIONc_mcbond_it1.6091.5
X-RAY DIFFRACTIONc_scbond_it2.3112
X-RAY DIFFRACTIONc_mcangle_it2.742
X-RAY DIFFRACTIONc_scangle_it3.2772.5
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1protein_rep.paramprotein.top
X-RAY DIFFRACTION2dna-rna_rep.paramdna-rna.top
X-RAY DIFFRACTION3water_rep.paramwater.top
X-RAY DIFFRACTION4ion.paramion.top
X-RAY DIFFRACTION5BI00201335_mod.parBI00201335_mod.top

+
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