4H4M

Crystal Structure of HIV-1 Reverse Transcriptase in Complex with (E)-3-(3-chloro-5-(4-chloro-2-(2-(2,4-dioxo-3,4- dihydropyrimidin-1(2H)-yl)ethoxy)phenoxy)phenyl)acrylonitrile (JLJ494), a Non-nucleoside Inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.233 

Starting Model: experimental
View more details

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history. 


Literature

Crystal Structures of HIV-1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design.

Frey, K.M., Bollini, M., Mislak, A.C., Cisneros, J.A., Gallardo-Macias, R., Jorgensen, W.L., Anderson, K.S.

(2012) J Am Chem Soc 134: 19501-19503

  • DOI: https://doi.org/10.1021/ja3092642
  • Primary Citation of Related Structures:  
    4H4M, 4H4O

  • PubMed Abstract: 

    X-ray crystal structures at 2.9 Å resolution are reported for two complexes of catechol diethers with HIV-1 reverse transcriptase. The results help elucidate the structural origins of the extreme antiviral activity of the compounds. The possibility of halogen bonding between the inhibitors and Pro95 is addressed. Structural analysis reveals key interactions with conserved residues P95 and W229 of importance for design of inhibitors with high potency and favorable resistance profiles.

    • Organizational Affiliation: 

    Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, United States.


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Reverse transcriptase/ribonuclease H, Exoribonuclease H, p66 RT557Human immunodeficiency virus type 1 BH10Mutation(s): 3 
Gene Names: p66 RT
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data), 3.1.26.13 (PDB Primary Data), 3.1.13.2 (PDB Primary Data)
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Reverse transcriptase/ribonuclease H, Exoribonuclease H, p51 RT428Human immunodeficiency virus type 1 BH10Mutation(s): 1 
Gene Names: p51 RT
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data), 3.1.26.13 (PDB Primary Data), 3.1.13.2 (PDB Primary Data)
UniProt
Find proteins for P03366 (Human immunodeficiency virus type 1 group M subtype B (isolate BH10))
Explore P03366 
Go to UniProtKB:  P03366
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03366
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
494
Query on 494
Download Ideal Coordinates CCD File 
C [auth A](2E)-3-(3-chloro-5-{4-chloro-2-[2-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)ethoxy]phenoxy}phenyl)prop-2-enenitrile
C21 H15 Cl2 N3 O4
LXPGWIGXHHBGJC-OWOJBTEDSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
D [auth B]1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
494 BindingDB:  4H4M IC50: 3 (nM) from 1 assay(s)
PDBBind:  4H4M IC50: 3 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.85 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.233 
  • R-Value Observed: 0.233 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 225.133α = 90
b = 69.208β = 106.43
c = 104.138γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
CBASSdata collection
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


View more in-depth experimental data
Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-12-05
    Type: Initial release
  • Version 1.1: 2013-01-02
    Changes: Database references
  • Version 1.2: 2017-11-15
    Changes: Refinement description
  • Version 1.3: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description