2R5B

Structure of the gp41 N-trimer in complex with the HIV entry inhibitor PIE7


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Potent D-peptide inhibitors of HIV-1 entry

Welch, B.D.Vandemark, A.P.Heroux, A.Hill, C.P.Kay, M.S.

(2007) Proc Natl Acad Sci U S A 104: 16828-16833

  • DOI: https://doi.org/10.1073/pnas.0708109104
  • Primary Citation of Related Structures:  
    2R3C, 2R5B, 2R5D

  • PubMed Abstract: 

    During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC(50) = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS.


  • Organizational Affiliation

    Department of Biochemistry, University of Utah, Emma Eccles Jones Medical Research Building, 15 North Medical Drive East, Salt Lake City, UT 84112-5650, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
gp41 N-peptide
A, B, C
47synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
HIV entry inhibitor PIE7D [auth H],
E [auth K],
F [auth L]
17synthetic constructMutation(s): 0 
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.203 
  • R-Value Observed: 0.209 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 47.024α = 90
b = 106.201β = 90
c = 76.7γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-10-02
    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: 2017-10-25
    Changes: Refinement description, Source and taxonomy