3N3I

Crystal Structure of G48V/C95F tethered HIV-1 Protease/Saquinavir complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Insights into the mechanism of drug resistance: X-ray structure analysis of G48V/C95F tethered HIV-1 protease dimer/saquinavir complex

Prashar, V.Bihani, S.C.Das, A.Rao, D.R.Hosur, M.V.

(2010) Biochem Biophys Res Commun 396: 1018-1023

  • DOI: https://doi.org/10.1016/j.bbrc.2010.05.049
  • Primary Citation of Related Structures:  
    3N3I

  • PubMed Abstract: 

    The mutation G48V in HIV-1 protease is a major resistance mutation against the drug saquinavir. Recently, G48V mutation is found to co-exist with the mutation C95F in AIDS patients treated with saquinavir. We report here the three-dimensional crystal structure of G48V/C95F tethered HIV-1 protease/saquinavir complex. The structure indicates following as the possible causes of drug resistance: (1) loss of direct van der Waals interactions between saquinavir and enzyme residues PHE-53 and PRO-1081, (2) loss of water-mediated hydrogen bonds between the carbonyl oxygen atoms in saquinavir and amide nitrogen atoms of flap residues 50 and 1050, (3) changes in inter-monomer interactions, which could affect the energetics of domain movements associated with inhibitor-binding, and (4) significant reduction in the stability of the mutant dimer. The present structure also provides a rationale for the clinical observation that the resistance mutations C95F/G48V/V82A occur as a cluster in AIDS patients.


  • Organizational Affiliation

    Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protease203HIV-1 M:B_HXB2RMutation(s): 4 
Gene Names: gag-pol
EC: 3.4.23.16
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
ROC
Query on ROC

Download Ideal Coordinates CCD File 
B [auth A](2S)-N-[(2S,3R)-4-[(2S,3S,4aS,8aS)-3-(tert-butylcarbamoyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3-hydroxy-1 -phenyl-butan-2-yl]-2-(quinolin-2-ylcarbonylamino)butanediamide
C38 H50 N6 O5
QWAXKHKRTORLEM-UGJKXSETSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
ROC BindingDB:  3N3I Ki: min: 0.04, max: 117 (nM) from 17 assay(s)
Kd: min: 0.31, max: 67 (nM) from 3 assay(s)
IC50: min: 0.2, max: 270 (nM) from 16 assay(s)
-TΔS: min: -7.74e+1, max: -2.80e+1 (kJ/mol) from 28 assay(s)
ΔH: min: -3.18e+1, max: 35.53 (kJ/mol) from 27 assay(s)
ΔG: min: -6.23e+1, max: -4.18e+1 (kJ/mol) from 26 assay(s)
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 
  • Space Group: P 61
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.41α = 90
b = 62.41β = 90
c = 83.26γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-06-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Atomic model, Database references, Derived calculations, Non-polymer description, Structure summary, Version format compliance
  • Version 1.2: 2012-12-12
    Changes: Other
  • Version 1.3: 2017-08-09
    Changes: Source and taxonomy
  • Version 1.4: 2024-03-20
    Changes: Data collection, Database references, Derived calculations, Structure summary