2HB2

Structure of HIV protease 6X mutant in apo form


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.291 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.291 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Conformational flexibility in the flap domains of ligand-free HIV protease.

Heaslet, H.Rosenfeld, R.Giffin, M.Lin, Y.C.Tam, K.Torbett, B.E.Elder, J.H.McRee, D.E.Stout, C.D.

(2007) Acta Crystallogr D Biol Crystallogr 63: 866-875

  • DOI: https://doi.org/10.1107/S0907444907029125
  • Primary Citation of Related Structures:  
    2HB2, 2HB4, 2PC0

  • PubMed Abstract: 

    The crystal structures of wild-type HIV protease (HIV PR) in the absence of substrate or inhibitor in two related crystal forms at 1.4 and 2.15 A resolution are reported. In one crystal form HIV PR adopts an 'open' conformation with a 7.7 A separation between the tips of the flaps in the homodimer. In the other crystal form the tips of the flaps are 'curled' towards the 80s loop, forming contacts across the local twofold axis. The 2.3 A resolution crystal structure of a sixfold mutant of HIV PR in the absence of substrate or inhibitor is also reported. The mutant HIV PR, which evolved in response to treatment with the potent inhibitor TL-3, contains six point mutations relative to the wild-type enzyme (L24I, M46I, F53L, L63P, V77I, V82A). In this structure the flaps also adopt a 'curled' conformation, but are separated and not in contact. Comparison of the apo structures to those with TL-3 bound demonstrates the extent of conformational change induced by inhibitor binding, which includes reorganization of the packing between twofold-related flaps. Further comparison with six other apo HIV PR structures reveals that the 'open' and 'curled' conformations define two distinct families in HIV PR. These conformational states include hinge motion of residues at either end of the flaps, opening and closing the entire beta-loop, and translational motion of the flap normal to the dimer twofold axis and relative to the 80s loop. The alternate conformations also entail changes in the beta-turn at the tip of the flap. These observations provide insight into the plasticity of the flap domains, the nature of their motions and their critical role in binding substrates and inhibitors.


  • Organizational Affiliation

    Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protease99Human immunodeficiency virus 1Mutation(s): 8 
Gene Names: gal-pol
EC: 3.4.23.16
UniProt
Find proteins for Q9E3M8 (Human immunodeficiency virus 1)
Explore Q9E3M8 
Go to UniProtKB:  Q9E3M8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9E3M8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.291 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.291 
  • Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 49.671α = 90
b = 49.671β = 90
c = 109.613γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
MOSFLMdata reduction
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-06-26
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Advisory, Refinement description
  • Version 1.4: 2021-10-20
    Changes: Advisory, Database references
  • Version 1.5: 2024-02-14
    Changes: Data collection