[English] 日本語
Yorodumi
- PDB-6ul5: Crystal structure of HIV-1 reverse transcriptase (RT) in complex ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6ul5
TitleCrystal structure of HIV-1 reverse transcriptase (RT) in complex with 4-[(4-{4-[(E)-2-cyanoethenyl]-2,6-dimethylphenoxy}thieno[3,2-d]pyrimidin-2-yl)amino]-2-fluorobenzonitrile (24b), a non-nucleoside RT inhibitor
Components(Reverse transcriptase ...) x 2
KeywordsTRANSFERASE / Human immunodeficiency virus 1 / non nucleotide-reverse transcriptase inhibitor
Function / homology
Function and homology information


RNA-directed DNA polymerase activity / HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase ...RNA-directed DNA polymerase activity / HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / host multivesicular body / DNA integration / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency / telomerase activity / viral penetration into host nucleus / RNA stem-loop binding / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / host cell / viral nucleocapsid / DNA recombination / DNA-directed DNA polymerase / aspartic-type endopeptidase activity / Hydrolases; Acting on ester bonds / DNA-directed DNA polymerase activity / symbiont-mediated suppression of host gene expression / symbiont entry into host cell / viral translational frameshifting / lipid binding / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity / proteolysis / DNA binding / zinc ion binding / membrane
Similarity search - Function
HIV Type 1 Reverse Transcriptase, subunit A, domain 1 / HIV Type 1 Reverse Transcriptase; Chain A, domain 1 / Reverse transcriptase/Diguanylate cyclase domain / Ribonuclease H-like superfamily/Ribonuclease H / Reverse transcriptase connection / Reverse transcriptase connection domain / Reverse transcriptase thumb / Reverse transcriptase thumb domain / Integrase Zinc binding domain / Zinc finger integrase-type profile. ...HIV Type 1 Reverse Transcriptase, subunit A, domain 1 / HIV Type 1 Reverse Transcriptase; Chain A, domain 1 / Reverse transcriptase/Diguanylate cyclase domain / Ribonuclease H-like superfamily/Ribonuclease H / 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. / Retropepsin-like catalytic domain / Matrix protein, lentiviral and alpha-retroviral, N-terminal / Retroviral nucleocapsid Gag protein p24, C-terminal domain / Gag protein p24 C-terminal domain / RNase H type-1 domain profile. / Ribonuclease H domain / Retropepsins / Retroviral aspartyl protease / Aspartyl protease, retroviral-type family profile. / Peptidase A2A, retrovirus, catalytic / Reverse transcriptase domain / Reverse transcriptase (RNA-dependent DNA polymerase) / Reverse transcriptase (RT) catalytic domain profile. / 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. / Nucleotidyltransferase; domain 5 / Aspartic peptidase, active site / Eukaryotic and viral aspartyl proteases active site. / Aspartic peptidase domain superfamily / Ribonuclease H superfamily / Ribonuclease H-like superfamily / Reverse transcriptase/Diguanylate cyclase domain / Alpha-Beta Plaits / Roll / DNA/RNA polymerase superfamily / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-QAG / Gag-Pol polyprotein
Similarity search - Component
Biological speciesHuman immunodeficiency virus type 1
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.23 Å
AuthorsRuiz, F.X. / Pilch, A. / Arnold, E.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)MERIT Award R37 AI027690 United States
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery and Characterization of Fluorine-Substituted Diarylpyrimidine Derivatives as Novel HIV-1 NNRTIs with Highly Improved Resistance Profiles and Low Activity for the hERG Ion Channel.
Authors: Kang, D. / Ruiz, F.X. / Feng, D. / Pilch, A. / Zhao, T. / Wei, F. / Wang, Z. / Sun, Y. / Fang, Z. / De Clercq, E. / Pannecouque, C. / Arnold, E. / Liu, X. / Zhan, P.
History
DepositionOct 6, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 5, 2020Provider: repository / Type: Initial release
Revision 1.1Feb 26, 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.identifier_ORCID
Revision 1.2Oct 11, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Reverse transcriptase p66
B: Reverse transcriptase p51
hetero molecules


Theoretical massNumber of molelcules
Total (without water)115,59617
Polymers114,0862
Non-polymers1,51115
Water5,711317
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: 1 biological assembliy in the asymmetric unit: A,B
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area7870 Å2
ΔGint-117 kcal/mol
Surface area46800 Å2
MethodPISA
Unit cell
Length a, b, c (Å)162.488, 73.068, 109.085
Angle α, β, γ (deg.)90.000, 100.291, 90.000
Int Tables number5
Space group name H-MC121
Space group name HallC2y
Symmetry operation#1: x,y,z
#2: -x,y,-z
#3: x+1/2,y+1/2,z
#4: -x+1/2,y+1/2,-z
Components on special symmetry positions
IDModelComponents
11A-770-

HOH

-
Components

-
Reverse transcriptase ... , 2 types, 2 molecules AB

#1: Protein Reverse transcriptase p66


Mass: 63989.238 Da / Num. of mol.: 1 / Mutation: K172A, K173A, C280S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus type 1 / Production host: Escherichia coli (E. coli) / References: UniProt: P03366, RNA-directed DNA polymerase
#2: Protein Reverse transcriptase p51


Mass: 50096.539 Da / Num. of mol.: 1 / Mutation: C280S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus type 1 / Production host: Escherichia coli (E. coli) / References: UniProt: P03366

-
Non-polymers , 5 types, 332 molecules

#3: Chemical ChemComp-QAG / 4-[(4-{4-[(E)-2-cyanoethenyl]-2,6-dimethylphenoxy}thieno[3,2-d]pyrimidin-2-yl)amino]-2-fluorobenzonitrile


Mass: 441.480 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H16FN5OS / Feature type: SUBJECT OF INVESTIGATION
#4: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: SO4
#5: Chemical
ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C2H6O2
#6: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#7: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 317 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.79 Å3/Da / Density % sol: 55.95 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 6.3
Details: 10%(v/v) PEG 8000, 4%(v/v) PEG 400, 100 mM MES pH 6.3, 10 mM spermine, 15 mM MgSO4, 100 mM ammonium sulfate, and 5 mM tris(2-carboxyethyl)phosphine

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1.03 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Jul 28, 2019
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.03 Å / Relative weight: 1
ReflectionResolution: 2.23→50 Å / Num. obs: 59921 / % possible obs: 98.3 % / Redundancy: 7.4 % / Biso Wilson estimate: 43.39 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.123 / Rpim(I) all: 0.042 / Rrim(I) all: 0.131 / Net I/σ(I): 13.32
Reflection shellResolution: 2.23→2.28 Å / Redundancy: 2.2 % / Rmerge(I) obs: 0.642 / Mean I/σ(I) obs: 1.44 / Num. unique obs: 2520 / CC1/2: 0.221 / Rpim(I) all: 0.461 / Rrim(I) all: 0.759 / % possible all: 83.1

-
Processing

Software
NameVersionClassification
PHENIXdev_3051refinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4G1Q

4g1q


Resolution: 2.23→41.27 Å / SU ML: 0.3256 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 25.5478
RfactorNum. reflection% reflectionSelection details
Rfree0.2453 2000 3.34 %5 %
Rwork0.2107 ---
obs0.2118 59912 97.8 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso mean: 55.99 Å2
Refinement stepCycle: LAST / Resolution: 2.23→41.27 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7959 0 92 317 8368
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00438295
X-RAY DIFFRACTIONf_angle_d0.71711275
X-RAY DIFFRACTIONf_chiral_restr0.04481211
X-RAY DIFFRACTIONf_plane_restr0.00571448
X-RAY DIFFRACTIONf_dihedral_angle_d16.87843154
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.23-2.290.35051130.33493263X-RAY DIFFRACTION77.84
2.29-2.350.34441370.31373966X-RAY DIFFRACTION93.89
2.35-2.420.32661410.2954100X-RAY DIFFRACTION98.4
2.42-2.50.32531440.27934171X-RAY DIFFRACTION99.54
2.5-2.590.31021450.25294211X-RAY DIFFRACTION99.89
2.59-2.690.28211470.23784225X-RAY DIFFRACTION99.91
2.69-2.810.26321450.21954214X-RAY DIFFRACTION99.93
2.81-2.960.27611450.21984213X-RAY DIFFRACTION99.95
2.96-3.150.26821460.2224213X-RAY DIFFRACTION99.93
3.15-3.390.30561470.21614235X-RAY DIFFRACTION99.91
3.39-3.730.24911450.20264223X-RAY DIFFRACTION99.93
3.73-4.270.21931470.18034254X-RAY DIFFRACTION99.91
4.27-5.380.20561470.17824255X-RAY DIFFRACTION100
5.38-41.270.18311510.19224369X-RAY DIFFRACTION99.91

+
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