2FDD

Crystal structure of HIV protease D545701 bound with GW0385


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.58 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: The discovery of GW0385.

Miller, J.F.Andrews, C.W.Brieger, M.Furfine, E.S.Hale, M.R.Hanlon, M.H.Hazen, R.J.Kaldor, I.McLean, E.W.Reynolds, D.Sammond, D.M.Spaltenstein, A.Tung, R.Turner, E.M.Xu, R.X.Sherrill, R.G.

(2006) Bioorg Med Chem Lett 16: 1788-1794

  • DOI: https://doi.org/10.1016/j.bmcl.2006.01.035
  • Primary Citation of Related Structures:  
    2FDD, 2FDE

  • PubMed Abstract: 

    A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385.


  • Organizational Affiliation

    GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. john.6.miller@gsk.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Gag-Pol polyprotein
A, B
100Human immunodeficiency virus 1Mutation(s): 14 
EC: 3.4.23.16
UniProt
Find proteins for Q7SPG9 (Human immunodeficiency virus 1)
Explore Q7SPG9 
Go to UniProtKB:  Q7SPG9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ7SPG9
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
385
Query on 385

Download Ideal Coordinates CCD File 
C [auth B](3R,3AS,6AR)-HEXAHYDROFURO[2,3-B]FURAN-3-YL [(1S,2R)-3-[(1,3-BENZODIOXOL-5-YLSULFONYL)(ISOBUTYL)AMINO]-2-HYDROXY-1-{4-[(2-METHYL-1,3-THIAZOL-4-YL)METHOXY]BENZYL}PROPYL]CARBAMATE
C33 H41 N3 O10 S2
JORVRJNILJXMMG-OLNQLETPSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
385 BindingDB:  2FDD Ki: min: 1.50e-5, max: 3.40e-3 (nM) from 4 assay(s)
PDBBind:  2FDD IC50: 4.8 (nM) from 1 assay(s)
Binding MOAD:  2FDD IC50: 4.8 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.58 Å
  • R-Value Free: 0.236 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.217 
  • Space Group: P 41
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.382α = 90
b = 55.382β = 90
c = 79.169γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
HKL-2000data reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

  • Released Date: 2006-02-21 
  • Deposition Author(s): Xu, R.X.

Revision History  (Full details and data files)

  • Version 1.0: 2006-02-21
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references, Derived calculations
  • Version 1.4: 2024-02-14
    Changes: Data collection