[English] 日本語
Yorodumi
- PDB-7vlh: Crystal structure of Zika NS2B-NS3 protease with compound MI2219 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7vlh
TitleCrystal structure of Zika NS2B-NS3 protease with compound MI2219
Components
  • NS3 protease
  • Serine protease subunit NS2B
KeywordsVIRAL PROTEIN / NS3 Protease
Function / homology
Function and homology information


symbiont-mediated suppression of host interferon-mediated signaling pathway / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / 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 / double-stranded RNA binding / nucleoside-triphosphate phosphatase / symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of TBK1 activity ...symbiont-mediated suppression of host interferon-mediated signaling pathway / flavivirin / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of host TYK2 activity / 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 / double-stranded RNA binding / nucleoside-triphosphate phosphatase / 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 / protein-macromolecule adaptor activity / mRNA (guanine-N7)-methyltransferase / methyltransferase cap1 / clathrin-dependent endocytosis of virus by host cell / methyltransferase cap1 activity / mRNA 5'-cap (guanine-N7-)-methyltransferase activity / host cell cytoplasm / RNA helicase activity / protein dimerization activity / host cell perinuclear region of cytoplasm / host cell endoplasmic reticulum membrane / RNA helicase / symbiont-mediated suppression of host innate immune response / symbiont-mediated suppression of host type I interferon-mediated signaling pathway / symbiont entry into host cell / symbiont-mediated activation of host autophagy / RNA-directed RNA polymerase / serine-type endopeptidase activity / viral RNA genome replication / RNA-directed RNA polymerase activity / fusion of virus membrane with host endosome membrane / lipid binding / viral envelope / GTP binding / virion attachment to host cell / host cell nucleus / virion membrane / structural molecule activity / ATP hydrolysis activity / proteolysis / extracellular region / ATP binding / metal ion binding / membrane
Similarity search - Function
Flavivirus non-structural protein NS2B / Flavivirus capsid protein C superfamily / Genome polyprotein, Flavivirus / : / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / Flavivirus non-structural protein NS4B / Flavivirus non-structural protein NS4A ...Flavivirus non-structural protein NS2B / Flavivirus capsid protein C superfamily / Genome polyprotein, Flavivirus / : / Flavivirus non-structural protein NS4A / Flavivirus non-structural protein NS2B / Flavivirus non-structural protein NS4B / mRNA cap 0/1 methyltransferase / 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. / RNA-directed RNA polymerase, thumb domain, Flavivirus / Flavivirus RNA-directed RNA polymerase, thumb domain / RNA-directed RNA polymerase, flavivirus / Flavivirus RNA-directed RNA polymerase, fingers and palm domains / Flavivirus capsid protein C / Flavivirus capsid protein C / Flavivirus non-structural Protein NS1 / Flavivirus non-structural protein NS1 / Envelope glycoprotein M, flavivirus / Envelope glycoprotein M superfamily, flavivirus / Flavivirus envelope glycoprotein M / Flavivirus polyprotein propeptide / Flavivirus polyprotein propeptide superfamily / Flavivirus polyprotein propeptide / Flavivirus envelope glycoprotein E, stem/anchor domain / : / Flavivirus NS3 helicase, C-terminal helical domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain / Flavivirus envelope glycoprotein E, Stem/Anchor domain superfamily / Flavivirus glycoprotein E, immunoglobulin-like domain / Flavivirus glycoprotein, immunoglobulin-like domain / Flavivirus glycoprotein central and dimerisation domain / Flavivirus glycoprotein, central and dimerisation domains / Flaviviral glycoprotein E, central domain, subdomain 1 / Flaviviral glycoprotein E, central domain, subdomain 2 / 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 / Helicase superfamily 1/2, ATP-binding domain / 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 / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Chem-7Q3 / Genome polyprotein / Genome polyprotein
Similarity search - Component
Biological speciesZika virus
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.621 Å
AuthorsQuek, J.P.
Funding support Singapore, 1items
OrganizationGrant numberCountry
National Research Foundation (NRF, Singapore)NRF2016NRF-CRP001-063 Singapore
CitationJournal: J.Med.Chem. / Year: 2022
Title: Structure-Based Optimization and Characterization of Macrocyclic Zika Virus NS2B-NS3 Protease Inhibitors.
Authors: Huber, S. / Braun, N.J. / Schmacke, L.C. / Quek, J.P. / Murra, R. / Bender, D. / Hildt, E. / Luo, D. / Heine, A. / Steinmetzer, T.
History
DepositionOct 2, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 10, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.2Oct 23, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
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)25,5974
Polymers24,9032
Non-polymers6942
Water543
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3920 Å2
ΔGint-36 kcal/mol
Surface area8530 Å2
MethodPISA
Unit cell
Length a, b, c (Å)40.992, 40.992, 214.435
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number95
Space group name H-MP4322

-
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
#3: Chemical ChemComp-7Q3 / 1-[(3~{S},6~{R},18~{R})-3,6-bis(4-azanylbutyl)-2,5,8,11,14,17-hexakis(oxidanylidene)-1,4,7,10,13,16-hexazacyclodocos-18-yl]guanidine


Mass: 597.711 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H47N11O6 / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.81 Å3/Da / Density % sol: 31.99 %
Crystal growTemperature: 291.15 K / Method: vapor diffusion, hanging drop / Details: 2M Ammonium Sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Australian Synchrotron / Beamline: MX2 / Wavelength: 0.953726 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Oct 11, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.953726 Å / Relative weight: 1
ReflectionResolution: 2.62→40.26 Å / Num. obs: 6110 / % possible obs: 99.44 % / Redundancy: 12.1 % / CC1/2: 0.999 / Net I/σ(I): 16.55
Reflection shellResolution: 2.62→2.715 Å / Redundancy: 12.1 % / Num. unique obs: 580 / CC1/2: 0.947 / % possible all: 98.3

-
Processing

Software
NameVersionClassification
PHENIX1.16_3549refinement
Aimless0.7.4data scaling
PDB_EXTRACT3.27data extraction
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5GPI

5gpi


Resolution: 2.621→40.26 Å / SU ML: 0.2 / Cross valid method: THROUGHOUT / Phase error: 32.41 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2891 305 5.01 %
Rwork0.2387 5784 -
obs-6087 99.44 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 110.18 Å2 / Biso min: 30 Å2
Refinement stepCycle: final / Resolution: 2.621→40.26 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1339 0 93 3 1435
Biso mean--83.33 61.52 -
Num. residues----191
LS refinement shellResolution: 2.621→3.715 Å / Rfactor Rfree: 0.3619 / Rfactor Rwork: 0.3474 / Rfactor Rfree error: 0
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)
15.37123.73282.40335.35422.43945.5826-0.3611-0.0347-0.0287-0.75540.08340.4049-0.4009-1.37330.09730.6127-0.1111-0.02330.77480.0250.4378-25.10059.1803-17.8451
25.51011.7867-0.01428.3284-7.16316.6194-0.1347-0.25361.66710.0843-0.02-0.03941.79931.31780.22920.8839-0.2128-0.06660.8345-0.11490.4188-22.0691-5.6444-31.9606
35.6927-2.87675.51397.3049-1.5145.75350.04182.00860.5021-2.10310.9691-1.707-1.37111.0212-0.59831.0183-0.2460.28151.281-0.17360.6717-6.1334-7.7118-26.9836
48.9997-3.9445-5.81997.82021.62154.0053-0.6943-0.98720.70760.52281.0545-0.53221.56860.064-0.84820.6495-0.0175-0.14780.8036-0.0560.6209-2.7352-5.8001-7.2183
53.79213.2478-1.7079.6957-3.97252.38710.1060.270.15040.44890.13210.23240.0868-0.2485-0.15960.5645-0.0544-0.01330.6708-0.02420.3622-21.71886.997-14.3517
62.0793-0.44620.44023.55190.23296.8617-0.3655-1.24421.43950.70390.40750.2699-1.0073-1.10010.07430.8582-0.03290.13220.7453-0.12460.7404-26.533110.8686-7.5499
72.9859-0.81890.26091.02120.45673.7907-0.1872-0.0981-0.04430.09810.1670.00810.3571-0.0498-0.00230.4095-0.1207-0.04050.4573-0.01220.4084-19.2142-3.1699-14.6088
85.5828-4.22222.64717.0168-3.98163.7584-0.6779-0.89320.7517-0.0550.3007-1.80950.0889-0.9760.20060.5117-0.1459-0.08040.6063-0.0730.5532-10.0692-8.5037-22.9093
96.3414-0.78152.11367.63951.21642.548-0.3123-0.6824-0.42760.84540.18010.08180.1910.85550.17570.3879-0.12780.06240.6199-0.00180.264-10.4335-3.1602-18.2215
106.69450.67562.6563.51050.83651.51710.16491.0747-0.43830.20160.0714-0.20650.02590.2366-0.24330.6153-0.09280.07660.6833-0.05460.4303-11.4881-4.5509-19.5569
119.29033.89282.84522.834-1.0987.82741.2347-1.7054-0.47841.4929-0.45381.30820.9624-0.7526-1.00480.4994-0.15010.04910.7526-0.03470.6524-17.2464-8.135-12.1123
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 50 through 59 )A50 - 59
2X-RAY DIFFRACTION2chain 'A' and (resid 60 through 64 )A60 - 64
3X-RAY DIFFRACTION3chain 'A' and (resid 65 through 74 )A65 - 74
4X-RAY DIFFRACTION4chain 'A' and (resid 75 through 87 )A75 - 87
5X-RAY DIFFRACTION5chain 'B' and (resid 18 through 53 )B18 - 53
6X-RAY DIFFRACTION6chain 'B' and (resid 54 through 66 )B54 - 66
7X-RAY DIFFRACTION7chain 'B' and (resid 67 through 106 )B67 - 106
8X-RAY DIFFRACTION8chain 'B' and (resid 107 through 118 )B107 - 118
9X-RAY DIFFRACTION9chain 'B' and (resid 119 through 139 )B119 - 139
10X-RAY DIFFRACTION10chain 'B' and (resid 140 through 163 )B140 - 163
11X-RAY DIFFRACTION11chain 'B' and (resid 164 through 170 )B164 - 170

+
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