[English] 日本語
Yorodumi
- PDB-1fk9: CRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1fk9
TitleCRYSTAL STRUCTURE OF HIV-1 REVERSE TRANSCRIPTASE IN COMPLEX WITH DMP-266(EFAVIRENZ)
Components
  • HIV-1 RT, A-CHAIN
  • HIV-1 RT, B-CHAIN
KeywordsTRANSFERASE / HIV-1 reverse transcriptase / AIDS / non-nucleoside inhibitor / DMP-266 / Efavirenz / drug design
Function / homology
Function and homology information


integrase activity / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / Minus-strand DNA synthesis / Plus-strand DNA synthesis / Uncoating of the HIV Virion / 2-LTR circle formation / Vpr-mediated nuclear import of PICs / Early Phase of HIV Life Cycle / Integration of provirus ...integrase activity / Integration of viral DNA into host genomic DNA / Autointegration results in viral DNA circles / Minus-strand DNA synthesis / Plus-strand DNA synthesis / Uncoating of the HIV Virion / 2-LTR circle formation / Vpr-mediated nuclear import of PICs / Early Phase of HIV Life Cycle / Integration of provirus / APOBEC3G mediated resistance to HIV-1 infection / Binding and entry of HIV virion / viral life cycle / HIV-1 retropepsin / symbiont-mediated activation of host apoptosis / retroviral ribonuclease H / exoribonuclease H / exoribonuclease H activity / Assembly Of The HIV Virion / Budding and maturation of HIV virion / protein processing / viral genome integration into host DNA / RNA-directed DNA polymerase / establishment of integrated proviral latency / RNA stem-loop binding / host multivesicular body / viral penetration into host nucleus / RNA-directed DNA polymerase activity / RNA-DNA hybrid ribonuclease activity / Transferases; Transferring phosphorus-containing groups; Nucleotidyltransferases / peptidase activity / 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 / viral translational frameshifting / lipid binding / symbiont entry into host cell / host cell nucleus / host cell plasma membrane / virion membrane / structural molecule activity / DNA binding / zinc ion binding / identical protein 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 / Retrovirus capsid, C-terminal / Reverse transcriptase domain / Reverse transcriptase (RNA-dependent DNA polymerase) / Reverse transcriptase (RT) catalytic domain profile. / 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-EFZ / Gag-Pol polyprotein
Similarity search - Component
Biological speciesHuman immunodeficiency virus 1
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 2.5 Å
AuthorsRen, J. / Milton, J. / Weaver, K.L. / Short, S.A. / Stuart, D.I. / Stammers, D.K.
Citation
Journal: STRUCTURE FOLD.DES. / Year: 2000
Title: Structural basis for the resilience of efavirenz (DMP-266) to drug resistance mutations in HIV-1 reverse transcriptase.
Authors: Ren, J. / Milton, J. / Weaver, K.L. / Short, S.A. / Stuart, D.I. / Stammers, D.K.
#1: Journal: J.Biol.Chem. / Year: 2000
Title: Binding of the second generattion non-nucleoside inhibitor S-1153 to HIV-1 reverse transcriptase involves extensive main chain hydrogen bonding
Authors: Ren, J. / Nichols, C. / Bird, L.E. / Fujiwara, T. / Suginoto, H. / Stuart, D.I. / Stammers, D.K.
#2: Journal: J.Biol.Chem. / Year: 2000
Title: Phenethylthiazolylthiourea (PETT) non-nucleoside inhibitors of HIV-1 and HIV-2 reverse transcriptases: structural and biochemical analyses
Authors: Ren, J. / Diprose, J. / Warren, J. / Esnouf, R.M. / Bird, L.E. / Ikemizu, S. / Slater, M. / Milton, J. / Balzarini, J. / Stuart, D.I. / Stammers, D.K.
#3: Journal: J.Med.Chem. / Year: 1999
Title: Crystallographic analysis of the binding modes of non-nucleoside thiazoloisoindolinone inhibitors to HIV-1 reverse transcriptase and comparison with modeling studies
Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Stuart, D.I. / Stammers, D.K.
#4: Journal: J.Med.Chem. / Year: 1999
Title: Design of MKC-442 (emivirine) analogues with improved activity against drug-resistant HIV mutants
Authors: Hopkins, A.L. / Ren, J. / Tanaka, H. / Baba, M. / Okamato, M. / Stuart, D.I. / Stammers, D.K.
#5: Journal: Biochemistry / Year: 1998
Title: Crystal structures of reverse transcriptase in complex with carboxanilide derivatives
Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Warren, J. / Balzarini, J. / Stuart, D.I. / Stammers, D.K.
#6: Journal: Proc.Natl.Acad.Sci.USA / Year: 1998
Title: 3'-azido-3'-deoxythymidine drug resistance mutations in HIV-1 reverse transcriptase can induce long range conformational changes
Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Jones, E.Y. / Kirby, I. / Keeling, J. / Ross, C.K. / Larder, B.A. / Stuart, D.I. / Stammers, D.K.
#7: Journal: Acta Crystallogr.,Sect.D / Year: 1998
Title: Continuous and discontinuous changes in the unit cell of HIV-1 reverse transcriptase crystals on dehydration
Authors: Esnouf, R.M. / Ren, J. / Garman, E. / Somers, D.O. / Ross, C.K. / Jones, E.Y. / Stammers, D.K. / Stuart, D.I.
#8: Journal: Proc.Natl.Acad.Sci.USA / Year: 1997
Title: Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this non-nucleoside inhibitor
Authors: Esnouf, R.M. / Ren, J. / Hopkins, A.L. / Ross, C.K. / Jones, E.Y. / Stammers, D.K. / Stuart, D.I.
#9: Journal: J.Med.Chem. / Year: 1996
Title: Complexes of HIV-1 reverse transcriptase with inhibitors of the HEPT series reveal conformational changes relevant to the design of potent non-nucleoside inhibitors
Authors: L Hopkins, A. / Ren, J. / Esnouf, R.M. / Willcox, B.E. / Jones, E.Y. / Ross, C.K. / Miyasaka, T. / Walker, R.T. / Tanaka, H. / Stammers, D.K. / Stuart, D.I.
#10: Journal: Structure / Year: 1995
Title: The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO: lessons for inhibitor design
Authors: Ren, J. / Esnouf, R.M. / Hopkins, A.L. / Ross, C.K. / Jones, E.Y. / K Stammers, D. / Stuart, D.I.
#11: Journal: Nat.Struct.Biol. / Year: 1995
Title: High Resolution Structures of HIV-1 RT From Four RT-inhibitor Complexes
Authors: Ren, J. / Esnouf, R.M. / Garman, E. / Somers, D.O. / Ross, C.K. / Kirby, I. / Keeling, J. / Darby, G. / Jones, E.Y. / Stuart, D.I. / Stammers, D.K.
#12: Journal: Nat.Struct.Biol. / Year: 1995
Title: Mechanism of Inhibition of HIV-1 Reverse Transcriptase by Non-nucleoside Inhibitors
Authors: Esnouf, R.M. / Ren, J. / Ross, C.K. / Jones, E.Y. / Stammers, D.K. / Stuart, D.I.
#13: Journal: J.Mol.Biol. / Year: 1994
Title: Crystals of HIV-1 Reverse Transcriptase Diffracting to 2.2 Angstrom Resolution
Authors: Stammers, D.K. / Somers, D.O. / Ross, C.K. / Kirby, I. / Ray, P.H. / Wilson, J.E. / Norman, M. / Ren, J. / Esnouf, R.M. / Garman, E. / Jones, E.Y. / Stuart, D.I.
History
DepositionAug 9, 2000Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 3, 2000Provider: repository / Type: Initial release
Revision 1.1Apr 27, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Jul 18, 2012Group: Non-polymer description
Revision 1.4Feb 1, 2017Group: Structure summary
Revision 1.5Oct 30, 2024Group: Data collection / Database references ...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 / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _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: HIV-1 RT, A-CHAIN
B: HIV-1 RT, B-CHAIN
hetero molecules


Theoretical massNumber of molelcules
Total (without water)114,4993
Polymers114,1832
Non-polymers3161
Water2,036113
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5420 Å2
ΔGint-29 kcal/mol
Surface area44140 Å2
MethodPISA
Unit cell
Length a, b, c (Å)139.8, 115.0, 65.4
Angle α, β, γ (deg.)90, 90, 90
Int Tables number19
Space group name H-MP212121
DetailsHIV-1 RT is a heterodimer consisting of a p66 and a p51 subunits, the p51 contains the first 440 residues of the p66.

-
Components

#1: Protein HIV-1 RT, A-CHAIN


Mass: 62783.824 Da / Num. of mol.: 1 / Fragment: P66
Source method: isolated from a genetically manipulated source
Details: COMPLEXED WITH DMP-266(EFAVIRENZ) / Source: (gene. exp.) Human immunodeficiency virus 1 / Genus: Lentivirus / Strain: HXB2 ISOLATE / Production host: Escherichia coli (E. coli) / References: UniProt: P04585, RNA-directed DNA polymerase
#2: Protein HIV-1 RT, B-CHAIN


Mass: 51399.047 Da / Num. of mol.: 1 / Fragment: P51
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human immunodeficiency virus 1 / Genus: Lentivirus / Strain: HXB2 ISOLATE / Production host: Escherichia coli (E. coli) / References: UniProt: P04585, RNA-directed DNA polymerase
#3: Chemical ChemComp-EFZ / (-)-6-CHLORO-4-CYCLOPROPYLETHYNYL-4-TRIFLUOROMETHYL-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONE / DMP-266 / Efavirenz


Mass: 315.675 Da / Num. of mol.: 1
Fragment: (-)-6-CHLORO-4-CYCLOPROPYLETHYNYL-4-TRIFLUOROMETHYL-1,4-DIHYDRO-2H-3,1-BENZOXAZIN-2-ONE
Source method: obtained synthetically / Formula: C14H9ClF3NO2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 113 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.3 Å3/Da / Density % sol: 46.54 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 5
Details: see reference 13, pH 5, VAPOR DIFFUSION, SITTING DROP, temperature 277K
Crystal grow
*PLUS
Temperature: 4 ℃ / pH: 5 / Details: Ren, J., (1998) Proc.Natl.Acad.Sci.USA, 95, 9518.
Components of the solutions
*PLUS
IDConc.Common nameCrystal-IDSol-ID
126 mg/mlenzyme1drop
26 %(w/v)PEG34001drop
36 %(w/v)PEG1reservoir
4citrate/phosphate1drop

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SRS / Beamline: PX7.2 / Wavelength: 1.488
DetectorType: MARRESEARCH / Detector: IMAGE PLATE / Date: Aug 10, 1997
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.488 Å / Relative weight: 1
ReflectionResolution: 2.5→30 Å / Num. obs: 31707 / % possible obs: 85.2 % / Observed criterion σ(I): -1.5 / Redundancy: 2.75 % / Biso Wilson estimate: 62 Å2 / Rmerge(I) obs: 0.062 / Net I/σ(I): 14.7
Reflection shellResolution: 2.5→2.59 Å / Redundancy: 2.2 % / Rmerge(I) obs: 0.363 / Num. unique all: 2682 / % possible all: 69.7
Reflection
*PLUS
Lowest resolution: 30 Å / Num. measured all: 87374
Reflection shell
*PLUS
% possible obs: 69.7 % / Num. unique obs: 2682

-
Processing

Software
NameClassification
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing
RefinementResolution: 2.5→30 Å / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.301 1541 5 %RANDOM
Rwork0.218 ---
obs0.214 31707 85.2 %-
Refinement stepCycle: LAST / Resolution: 2.5→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms7606 0 21 113 7740
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.008
X-RAY DIFFRACTIONc_angle_deg1.3
Software
*PLUS
Name: CNS / Version: 1 / Classification: refinement
Refinement
*PLUS
Highest resolution: 2.5 Å / Lowest resolution: 30 Å / σ(F): 0 / % reflection Rfree: 5 %
Solvent computation
*PLUS
Displacement parameters
*PLUS
Refine LS restraints
*PLUS
Type: c_angle_deg / Dev ideal: 1.3

+
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