[English] 日本語
Yorodumi
- PDB-8bv2: Biological and structural analysis of new potent Integrase-LEDGF ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8bv2
TitleBiological and structural analysis of new potent Integrase-LEDGF allosteric HIV-1 inhibitors
ComponentsIntegrase
KeywordsVIRAL PROTEIN / inhibitors / integrase / HIV-1
Function / homology
Function and homology information


HIV-1 retropepsin / : / retroviral ribonuclease H / exoribonuclease H / : / exoribonuclease H activity / host multivesicular body / DNA integration / RNA-directed DNA polymerase / viral genome integration into host DNA ...HIV-1 retropepsin / : / retroviral ribonuclease H / exoribonuclease H / : / exoribonuclease H activity / host multivesicular body / DNA integration / RNA-directed DNA polymerase / viral genome integration into host DNA / viral penetration into host nucleus / establishment of integrated proviral latency / RNA-directed DNA polymerase activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / RNA-DNA hybrid ribonuclease activity / viral nucleocapsid / DNA recombination / Hydrolases; Acting on ester bonds / DNA-directed DNA polymerase / aspartic-type endopeptidase activity / DNA-directed DNA polymerase activity / symbiont entry into host cell / symbiont-mediated suppression of host gene expression / lipid binding / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity / proteolysis / DNA binding / RNA binding / zinc ion binding / membrane
Similarity search - Function
Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. / Integrase-like, N-terminal / Integrase DNA binding domain / Integrase, C-terminal domain superfamily, retroviral / Integrase, N-terminal zinc-binding domain ...Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. / Integrase-like, N-terminal / Integrase DNA binding domain / Integrase, C-terminal domain superfamily, retroviral / Integrase, N-terminal zinc-binding domain / Integrase, C-terminal, retroviral / Integrase DNA binding domain profile. / Immunodeficiency lentiviral matrix, N-terminal / gag gene protein p17 (matrix protein) / RNase H / Integrase core domain / Integrase, catalytic core / Integrase catalytic domain profile. / Retroviral nucleocapsid Gag protein p24, C-terminal domain / Gag protein p24 C-terminal domain / Retropepsin-like catalytic domain / Matrix protein, lentiviral and alpha-retroviral, N-terminal / Ribonuclease H domain / RNase H type-1 domain profile. / Reverse transcriptase (RNA-dependent DNA polymerase) / Reverse transcriptase domain / Reverse transcriptase (RT) catalytic domain profile. / Retropepsins / Retroviral aspartyl protease / Aspartyl protease, retroviral-type family profile. / Peptidase A2A, retrovirus, catalytic / Retrovirus capsid, C-terminal / Retroviral matrix protein / Retrovirus capsid, N-terminal / zinc finger / Zinc knuckle / Zinc finger, CCHC-type superfamily / Zinc finger, CCHC-type / Zinc finger CCHC-type profile. / Ribonuclease H superfamily / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily / Ribonuclease H-like superfamily / Reverse transcriptase/Diguanylate cyclase domain / DNA/RNA polymerase superfamily
Similarity search - Domain/homology
Chem-RWR / Gag-Pol polyprotein
Similarity search - Component
Biological speciesHuman immunodeficiency virus 1
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2 Å
AuthorsRuff, M. / Benarous, R.
Funding support France, 1items
OrganizationGrant numberCountry
Other private France
CitationJournal: Antimicrob.Agents Chemother. / Year: 2023
Title: Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase.
Authors: Bonnard, D. / Le Rouzic, E. / Singer, M.R. / Yu, Z. / Le Strat, F. / Batisse, C. / Batisse, J. / Amadori, C. / Chasset, S. / Pye, V.E. / Emiliani, S. / Ledoussal, B. / Ruff, M. / Moreau, F. ...Authors: Bonnard, D. / Le Rouzic, E. / Singer, M.R. / Yu, Z. / Le Strat, F. / Batisse, C. / Batisse, J. / Amadori, C. / Chasset, S. / Pye, V.E. / Emiliani, S. / Ledoussal, B. / Ruff, M. / Moreau, F. / Cherepanov, P. / Benarous, R.
History
DepositionDec 1, 2022Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 7, 2023Provider: repository / Type: Initial release
Revision 1.1Jun 21, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jul 26, 2023Group: Database references / Category: citation / Item: _citation.journal_volume

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Integrase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)20,6554
Polymers20,1401
Non-polymers5153
Water1,838102
1
A: Integrase
hetero molecules

A: Integrase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,3098
Polymers40,2792
Non-polymers1,0306
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation6_554-x,-x+y,-z-2/31
Buried area3910 Å2
ΔGint-64 kcal/mol
Surface area11540 Å2
MethodPISA
Unit cell
Length a, b, c (Å)72.570, 72.570, 65.965
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121
Space group name HallP312"
Symmetry operation#1: x,y,z
#2: -y,x-y,z+1/3
#3: -x+y,-x,z+2/3
#4: x-y,-y,-z+2/3
#5: -x,-x+y,-z+1/3
#6: y,x,-z

-
Components

#1: Protein Integrase / / IN


Mass: 20139.646 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Gene: gag-pol / Production host: Escherichia coli (E. coli)
References: UniProt: P12497, Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases, Hydrolases; Acting on ester bonds
#2: Chemical ChemComp-RWR / (2S)-2-[3-cyclopropyl-2-(3,4-dihydro-2H-chromen-6-yl)-6-methyl-phenyl]-2-[(2-methylpropan-2-yl)oxy]ethanoic acid


Mass: 394.503 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H30O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


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


Mass: 18.015 Da / Num. of mol.: 102 / 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: 2.49 Å3/Da / Density % sol: 50.6 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 3 microliters of protein at 5 mg/mL in 50 mM MES pH5.5, 50 mM NaCl, 5 mM DTT mixed with 3 microliters of reservoir solution containing 0.1 M sodium cacodylate pH 6.5, 1.26 M ammonium sulfate.

-
Data collection

DiffractionMean temperature: 120 K / Serial crystal experiment: N
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-X / Wavelength: 1.5418 Å
DetectorType: DECTRIS EIGER R 4M / Detector: PIXEL / Date: Sep 15, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2→20 Å / Num. obs: 131582 / % possible obs: 100 % / Redundancy: 9.5 % / Biso Wilson estimate: 29.84 Å2 / CC1/2: 1 / CC star: 1 / Rmerge(I) obs: 0.0286 / Rpim(I) all: 0.01 / Rrim(I) all: 0.03 / Net I/σ(I): 57.43
Reflection shellResolution: 2→2.072 Å / Redundancy: 9.9 % / Rmerge(I) obs: 0.1985 / Mean I/σ(I) obs: 11.2 / Num. unique obs: 13489 / CC1/2: 0.986 / CC star: 0.997 / Rpim(I) all: 0.06627 / Rrim(I) all: 0.2094 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.20_4459refinement
XDSdata reduction
XDSdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2→19.97 Å / SU ML: 0.2016 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 23.9872
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2262 2555 9.89 %
Rwork0.1955 23287 -
obs0.1985 25842 98.58 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 31.65 Å2
Refinement stepCycle: LAST / Resolution: 2→19.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1020 0 35 102 1157
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00831075
X-RAY DIFFRACTIONf_angle_d1.02411461
X-RAY DIFFRACTIONf_chiral_restr0.0533166
X-RAY DIFFRACTIONf_plane_restr0.0065175
X-RAY DIFFRACTIONf_dihedral_angle_d9.227145
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2-2.040.27381460.22271275X-RAY DIFFRACTION100
2.04-2.080.27861480.2071320X-RAY DIFFRACTION100
2.08-2.130.20431420.19111347X-RAY DIFFRACTION100
2.13-2.170.25861400.18631301X-RAY DIFFRACTION100
2.18-2.230.34611390.25321216X-RAY DIFFRACTION94.29
2.23-2.290.34381210.33561100X-RAY DIFFRACTION83.23
2.29-2.360.33761400.20871302X-RAY DIFFRACTION100
2.36-2.430.27131460.21111313X-RAY DIFFRACTION100
2.43-2.520.21991480.2111321X-RAY DIFFRACTION99.93
2.52-2.620.24891420.21311289X-RAY DIFFRACTION99.86
2.62-2.740.27221410.19771350X-RAY DIFFRACTION99.87
2.74-2.880.23711440.22131310X-RAY DIFFRACTION100
2.88-3.060.20291480.20361311X-RAY DIFFRACTION99.86
3.06-3.30.21231380.1941319X-RAY DIFFRACTION99.93
3.3-3.630.18061470.17861312X-RAY DIFFRACTION99.79
3.63-4.150.16321450.16951260X-RAY DIFFRACTION97.77
4.15-5.20.21361380.1631328X-RAY DIFFRACTION100
5.22-19.970.23071420.1891313X-RAY DIFFRACTION99.93

+
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