5YB2

Crystal structure of LP-11/N44


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.80 Å
  • R-Value Free: 0.307 
  • R-Value Work: 0.283 
  • R-Value Observed: 0.284 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Insights into the Mechanisms of Action of Short-Peptide HIV-1 Fusion Inhibitors Targeting the Gp41 Pocket

Zhang, X.Zhu, Y.Hu, H.Zhang, S.Wang, P.Chong, H.He, J.Wang, X.He, Y.

(2018) Front Cell Infect Microbiol 8: 51-51

  • DOI: https://doi.org/10.3389/fcimb.2018.00051
  • Primary Citation of Related Structures:  
    5YB2, 5YB3, 5YB4

  • PubMed Abstract: 

    The deep hydrophobic pocket of HIV-1 gp41 has been considered a drug target, but short-peptides targeting this site usually lack potent antiviral activity. By applying the M-T hook structure, we previously generated highly potent short-peptide fusion inhibitors that specifically targeted the pocket site, such as MT-SC22EK, HP23L, and LP-11. Here, the crystal structures of HP23L and LP-11 bound to the target mimic peptide N36 demonstrated the critical intrahelical and interhelical interactions, especially verifying that the hook-like conformation was finely adopted while the methionine residue was replaced by the oxidation-less prone residue leucine, and that addition of an extra glutamic acid significantly enhanced the binding and inhibitory activities. The structure of HP23L bound to N36 with two mutations (E49K and L57R) revealed the critical residues and motifs mediating drug resistance and provided new insights into the mechanism of action of inhibitors. Therefore, the present data help our understanding for the structure-activity relationship (SAR) of HIV-1 fusion inhibitors and facilitate the development of novel antiviral drugs.


  • Organizational Affiliation

    College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoproteinA [auth E],
B [auth D],
G [auth B],
H [auth A],
M
67Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for P04578 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04578 
Go to UniProtKB:  P04578
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04578
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Envelope glycoproteinC [auth F],
I [auth C]
44Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for P04578 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04578 
Go to UniProtKB:  P04578
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP04578
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
LP-1123Human immunodeficiency virus 1Mutation(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: 3.80 Å
  • R-Value Free: 0.307 
  • R-Value Work: 0.283 
  • R-Value Observed: 0.284 
  • Space Group: H 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 110.884α = 90
b = 110.884β = 90
c = 125.382γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data processing
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-02-28
    Type: Initial release
  • Version 1.1: 2018-03-28
    Changes: Database references
  • Version 1.2: 2024-03-27
    Changes: Data collection, Database references