[English] 日本語
Yorodumi
- PDB-6kk2: Crystal structure of Zika NS2B-NS3 protease with compound 2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6kk2
TitleCrystal structure of Zika NS2B-NS3 protease with compound 2
Components
  • NS3 protease
  • Serine protease subunit NS2B
KeywordsVIRAL PROTEIN / Viral protease / Protease inhibitor complex
Function / homology
Function and homology information


symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / ribonucleoside triphosphate phosphatase activity / viral capsid / nucleoside-triphosphate phosphatase / double-stranded RNA binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / symbiont-mediated suppression of host toll-like receptor signaling pathway ...symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / ribonucleoside triphosphate phosphatase activity / viral capsid / nucleoside-triphosphate phosphatase / double-stranded RNA binding / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity / symbiont-mediated suppression of host toll-like receptor signaling pathway / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / mRNA (nucleoside-2'-O-)-methyltransferase activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / RNA helicase activity / host cell endoplasmic reticulum membrane / host cell perinuclear region of cytoplasm / protein dimerization activity / RNA helicase / induction by virus of host autophagy / symbiont entry into host cell / RNA-directed RNA polymerase / viral RNA genome replication / RNA-dependent RNA polymerase activity / serine-type endopeptidase activity / fusion of virus membrane with host endosome membrane / viral envelope / lipid binding / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / host cell nucleus / virion attachment to host cell / GTP binding / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / membrane / metal ion binding
Similarity search - Function
Thrombin, subunit H - #120 / : / Flavivirus envelope glycoprotein E, stem/anchor domain / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / Flavivirus capsid protein C superfamily / : / Flavivirus non-structural protein NS2B / Flavivirus NS3 helicase, C-terminal helical domain / Genome polyprotein, Flavivirus ...Thrombin, subunit H - #120 / : / Flavivirus envelope glycoprotein E, stem/anchor domain / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / Flavivirus capsid protein C superfamily / : / Flavivirus non-structural protein NS2B / Flavivirus NS3 helicase, C-terminal helical domain / Genome polyprotein, Flavivirus / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus capsid protein C / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A / Flavivirus NS2B domain profile. / mRNA cap 0 and cap 1 methyltransferase (EC 2.1.1.56 and EC 2.1.1.57) domain profile. / Flavivirus non-structural protein NS2A / Flavivirus non-structural protein NS2A / Flavivirus NS3, petidase S7 / Peptidase S7, Flavivirus NS3 serine protease / Flavivirus NS3 protease (NS3pro) domain profile. / Envelope glycoprotein M, flavivirus / Flavivirus envelope glycoprotein M / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M superfamily, flavivirus / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Ribosomal RNA methyltransferase, FtsJ domain / FtsJ-like methyltransferase / Flavivirus/Alphavirus glycoprotein, immunoglobulin-like domain superfamily / Flavivirus glycoprotein, central and dimerisation domain superfamily / Flaviviral glycoprotein E, dimerisation domain / DEAD box, Flavivirus / Flavivirus DEAD domain / helicase superfamily c-terminal domain / Immunoglobulin E-set / 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 / Trypsin-like serine proteases / Helicase superfamily 1/2, ATP-binding domain / Thrombin, subunit H / RNA-directed RNA polymerase, catalytic domain / RdRp of positive ssRNA viruses catalytic domain profile. / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Peptidase S1, PA clan / DNA/RNA polymerase superfamily / Beta Barrel / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta
Similarity search - Domain/homology
Chem-D9U / Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesZika virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.02 Å
AuthorsQuek, J.P.
Funding support Singapore, 3items
OrganizationGrant numberCountry
Other governmentStart up grant Singapore
Other governmentCBRG15May045 Singapore
Other governmentNRF2016NRF-CRP001-063 Singapore
CitationJournal: Chemmedchem / Year: 2020
Title: Structure-Based Macrocyclization of Substrate Analogue NS2B-NS3 Protease Inhibitors of Zika, West Nile and Dengue viruses.
Authors: Braun, N.J. / Quek, J.P. / Huber, S. / Kouretova, J. / Rogge, D. / Lang-Henkel, H. / Cheong, E.Z.K. / Chew, B.L.A. / Heine, A. / Luo, D. / Steinmetzer, T.
History
DepositionJul 23, 2019Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jun 17, 2020Provider: repository / Type: Initial release
Revision 1.1Aug 19, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Nov 22, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine protease subunit NS2B
B: NS3 protease
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,5623
Polymers24,9032
Non-polymers6591
Water68538
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4100 Å2
ΔGint-26 kcal/mol
Surface area9220 Å2
MethodPISA
Unit cell
Length a, b, c (Å)42.413, 42.413, 215.689
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number95
Space group name H-MP4322
Symmetry operation#1: x,y,z
#2: -y,x,z+3/4
#3: y,-x,z+1/4
#4: x,-y,-z+1/2
#5: -x,y,-z
#6: -x,-y,z+1/2
#7: y,x,-z+1/4
#8: -y,-x,-z+3/4
Components on special symmetry positions
IDModelComponents
11B-323-

HOH

-
Components

#1: Protein Serine protease subunit NS2B / / NS2B cofactor


Mass: 5865.384 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Zika virus / Production host: Escherichia coli (E. coli)
References: UniProt: Q32ZE1, flavivirin, nucleoside-triphosphate phosphatase, RNA helicase, mRNA (guanine-N7)-methyltransferase, methyltransferase cap1, RNA-directed RNA polymerase
#2: Protein NS3 protease


Mass: 19037.592 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Zika virus (strain Mr 766) / Strain: Mr 766 / Gene: GP1, A2G93_63394gpGP1 / Production host: Escherichia coli (E. coli) / References: UniProt: A0A142IX72, UniProt: Q32ZE1*PLUS
#3: Chemical ChemComp-D9U / 1-[(10~{S},17~{S},20~{S})-17,20-bis(4-azanylbutyl)-4,9,16,19,22-pentakis(oxidanylidene)-3,8,15,18,21-pentazabicyclo[22.2.2]octacosa-1(27),24(28),25-trien-10-yl]guanidine


Mass: 658.835 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C32H54N10O5 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 38 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.95 Å3/Da / Density % sol: 36.84 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop
Details: 0.2M Ammonium Sulfate, 0.1M Sodium acetate trihydrate 4.6, 25% PEG 4000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.95372 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Jul 2, 2018
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.95372 Å / Relative weight: 1
ReflectionResolution: 2.02→42.4 Å / Num. obs: 13825 / % possible obs: 99.4 % / Redundancy: 13.7 % / CC1/2: 0.999 / Rmerge(I) obs: 0.196 / Net I/σ(I): 35.1
Reflection shellResolution: 2.02→2.1 Å / Redundancy: 12.8 % / Rmerge(I) obs: 0.593 / Mean I/σ(I) obs: 3 / Num. unique obs: 1265 / CC1/2: 0.96 / % possible all: 95.2

-
Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
iMOSFLMdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5GPI

5gpi


Resolution: 2.02→42.4 Å / Cross valid method: NONE
RfactorNum. reflection% reflection
Rfree0.256 689 5.01 %
Rwork0.219 --
obs-13825 99.4 %
Displacement parametersBiso max: 101.88 Å2 / Biso min: 24.22 Å2
Refinement stepCycle: final / Resolution: 2.02→42.4 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1431 0 47 38 1516
Biso mean--65.22 49.21 -
Num. residues----193
LS refinement shellResolution: 2.02→2.09 Å /
RfactorNum. reflection
Rfree0.298 61
Rwork0.235 -
Refinement TLS params.

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 °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
14.67860.4840.58388.60093.557.58350.44460.503-0.00340.5306-0.61130.5770.0765-1.2497-0.2060.36540.0458-0.01960.41220.020.3471-26.35069.8197-18.6458
22.38610.24140.71.82750.40622.4380.07730.06770.1458-0.6183-0.097-0.35040.08610.6056-0.01490.65070.09360.11050.5829-0.09520.4215-8.6585-5.5092-19.1788
33.715-0.21111.81912.76091.44293.9284-0.05660.06390.8887-0.436-0.22670.86120.1585-0.8072-0.02130.5748-0.066-0.01430.37970.03370.3513-27.30259.1963-17.7159
43.50782.1215-0.64764.196-0.39261.96770.4675-0.16620.52280.1059-0.47970.5048-0.1403-0.29-0.12040.4137-0.00960.0120.253-0.02290.3617-20.402913.4744-15.3792
53.2324-0.2661-0.38772.12290.48912.5464-0.27940.1320.3689-0.02670.30760.1519-0.6137-0.1358-0.08570.3653-0.01560.05050.27920.02210.3461-23.48167.2599-9.3768
63.85850.1976-0.19061.6808-0.11672.68970.46060.3627-0.15190.4616-0.13360.1198-0.31560.0213-0.06280.4487-0.02740.06130.2312-0.00660.3258-22.57542.8378-4.653
71.21920.1816-0.78011.63010.13092.3933-0.2750.6781-0.25380.1477-0.43230.32241.0155-0.42110.14040.4783-0.0359-0.00270.3151-0.01290.352-22.2432-9.0408-16.4069
83.07070.5282-0.89254.82960.4552.71410.37860.98240.3417-0.4883-0.3957-0.4224-0.0564-0.3296-0.11830.36270.04040.02350.34950.0470.391-18.35915.3151-26.4824
91.77220.5285-0.07931.35710.97840.6373-0.04020.292-0.1139-0.1051-0.00480.0879-0.13260.05920.02540.3513-0.02170.0480.3926-0.02740.3253-10.9629-4.4839-20.1229
104.0803-0.59340.28612.6921.44283.74980.1687-0.24710.1014-0.36760.0240.0042-0.07420.2585-0.17610.406-0.05530.05990.247-0.00670.3018-14.7877-4.2829-17.8777
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 50 through 60 )A50 - 60
2X-RAY DIFFRACTION2chain 'A' and (resid 61 through 87 )A61 - 87
3X-RAY DIFFRACTION3chain 'B' and (resid 17 through 27 )B17 - 27
4X-RAY DIFFRACTION4chain 'B' and (resid 28 through 42 )B28 - 42
5X-RAY DIFFRACTION5chain 'B' and (resid 43 through 62 )B43 - 62
6X-RAY DIFFRACTION6chain 'B' and (resid 63 through 79 )B63 - 79
7X-RAY DIFFRACTION7chain 'B' and (resid 80 through 94 )B80 - 94
8X-RAY DIFFRACTION8chain 'B' and (resid 95 through 106 )B95 - 106
9X-RAY DIFFRACTION9chain 'B' and (resid 107 through 137 )B107 - 137
10X-RAY DIFFRACTION10chain 'B' and (resid 138 through 171 )B138 - 171

+
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