3C6U

Crystal Structure of HIV Reverse Transcriptase in complex with inhibitor 22


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.198 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations.

Tucker, T.J.Saggar, S.Sisko, J.T.Tynebor, R.M.Williams, T.M.Felock, P.J.Flynn, J.A.Lai, M.T.Liang, Y.McGaughey, G.Liu, M.Miller, M.Moyer, G.Munshi, V.Perlow-Poehnelt, R.Prasad, S.Sanchez, R.Torrent, M.Vacca, J.P.Wan, B.L.Yan, Y.

(2008) Bioorg Med Chem Lett 18: 2959-2966

  • DOI: https://doi.org/10.1016/j.bmcl.2008.03.064
  • Primary Citation of Related Structures:  
    3C6T, 3C6U

  • PubMed Abstract: 

    Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Research Laboratories, WP14-3, 770 Sumneytown Pike, PO Box 4, West Point, PA 19486-0004, USA. tom_tucker@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Reverse transcriptase563HIV-1 M:B_HXB2RMutation(s): 0 
Gene Names: gag-pol
EC: 2.7.7.49 (PDB Primary Data), 2.7.7.7 (PDB Primary Data)
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04585 
Go to UniProtKB:  P04585
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04585
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Reverse transcriptase443HIV-1 M:B_HXB2RMutation(s): 0 
Gene Names: gag-pol
UniProt
Find proteins for P04585 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04585 
Go to UniProtKB:  P04585
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04585
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
M22
Query on M22

Download Ideal Coordinates CCD File 
C [auth A]3-chloro-5-[2-chloro-5-(1H-indazol-3-ylmethoxy)phenoxy]benzonitrile
C21 H13 Cl2 N3 O2
WHCLIFOVZDANCU-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
M22 PDBBind:  3C6U IC50: 1.35 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.275 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.198 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 118.75α = 90
b = 154.2β = 90
c = 156.15γ = 90
Software Package:
Software NamePurpose
BUSTER-TNTrefinement
ADSCdata collection
HKL-2000data reduction
HKL-2000data scaling
BUSTERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description