4DVR

Crystal structure of YU2 gp120 core in complex with Fab 48d and NBD-557


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.289 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.233 

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Ligand Structure Quality Assessment 


This is version 1.6 of the entry. See complete history


Literature

Crystal Structures of HIV-1 gp120 Envelope Glycoprotein in Complex with NBD Analogues That Target the CD4-Binding Site.

Kwon, Y.D.Lalonde, J.M.Yang, Y.Elban, M.A.Sugawara, A.Courter, J.R.Jones, D.M.Smith, A.B.Debnath, A.K.Kwong, P.D.

(2014) PLoS One 9: e85940-e85940

  • DOI: https://doi.org/10.1371/journal.pone.0085940
  • Primary Citation of Related Structures:  
    4DVR, 4DVS, 4DVT, 4DVV, 4DVW, 4DVX

  • PubMed Abstract: 

    Efforts to develop therapeutic agents that inhibit HIV-1 entry have led to the identification of several small molecule leads. One of the most promising is the NBD series, which binds within a conserved gp120 cavity and possesses para-halogen substituted aromatic rings, a central oxalamide linker, and a tetramethylpiperidine moiety. In this study, we characterized structurally the interactions of four NBD analogues containing meta-fluoro substitution on the aromatic ring and various heterocyclic ring replacements of the tetramethylpiperidine group. The addition of a meta-fluorine to the aromatic ring improved surface complementarity and did not alter the position of the analogue relative to gp120. By contrast, heterocyclic ring replacements of the tetramethylpiperidine moiety exhibited diverse positioning and interactions with the vestibule of the gp120 cavity. Overall, the biological profile of NBD-congeners was modulated by ligand interactions with the gp120-cavity vestibule. Herein, six co-crystal structures of NBD-analogues with gp120 provide a structural framework for continued small molecule-entry inhibitor optimization.


  • Organizational Affiliation

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoprotein gp120A [auth G]313Human immunodeficiency virus type 1 (isolate YU2)Mutation(s): 0 
Gene Names: env
UniProt
Find proteins for P35961 (Human immunodeficiency virus type 1 group M subtype B (isolate YU-2))
Explore P35961 
Go to UniProtKB:  P35961
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35961
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Fab 48d Light chainB [auth L]212Homo sapiensMutation(s): 0 
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Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Fab 48d Heavy chainC [auth H]219Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.289 
  • R-Value Work: 0.228 
  • R-Value Observed: 0.233 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 53.445α = 90
b = 109.738β = 90
c = 130.682γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data collection
HKL-2000data reduction
HKL-2000data scaling
PHASESphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-02-27
    Type: Initial release
  • Version 1.1: 2014-03-19
    Changes: Database references
  • Version 1.2: 2014-12-17
    Changes: Non-polymer description
  • Version 1.3: 2017-05-31
    Changes: Structure summary
  • Version 1.4: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.5: 2021-05-19
    Changes: Source and taxonomy, Structure summary
  • Version 1.6: 2023-09-13
    Changes: Advisory, Data collection, Database references, Refinement description