5W6T

Crystal structure of the A/Puerto Rico/8/1934 (H1N1) influenza virus hemagglutinin in complex with cyclic peptide CP151070 (P7)

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.59 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 

Starting Model: experimental
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This is version 3.0 of the entry. See complete history. 


Literature

Potent peptidic fusion inhibitors of influenza virus.

Kadam, R.U., Juraszek, J., Brandenburg, B., Buyck, C., Schepens, W.B.G., Kesteleyn, B., Stoops, B., Vreeken, R.J., Vermond, J., Goutier, W., Tang, C., Vogels, R., Friesen, R.H.E., Goudsmit, J., van Dongen, M.J.P., Wilson, I.A.

(2017) Science 358: 496-502

  • DOI: https://doi.org/10.1126/science.aan0516
  • Primary Citation of Related Structures:  
    5W5S, 5W5U, 5W6I, 5W6R, 5W6T, 5W6U

  • PubMed Abstract: 

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH-induced conformational rearrangements associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule- and peptide-based therapeutics against influenza virus.

    • Organizational Affiliation: 

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin326Influenza A virus (A/Puerto Rico/8/1934(H1N1))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for P03452 (Influenza A virus (strain A/Puerto Rico/8/1934 H1N1))
Explore P03452 
Go to UniProtKB:  P03452
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03452
Glycosylation
Glycosylation Sites: 3
Sequence Annotations
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  • Reference Sequence
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(by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin176Influenza A virus (A/Puerto Rico/8/1934(H1N1))Mutation(s): 0 
Gene Names: HA
UniProt
Find proteins for P03452 (Influenza A virus (strain A/Puerto Rico/8/1934 H1N1))
Explore P03452 
Go to UniProtKB:  P03452
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03452
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
ACE-PH8-ORN-MLE-GLU-TYR-ZCL-GLU-TRP-LEU-SER-9WVC [auth F]12synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 4
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseD [auth C]2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Modified Residues  4 Unique
IDChains TypeFormula2D DiagramParent
9WV
Query on 9WV		C [auth F]L-PEPTIDE LINKINGC6 H13 N3 O3ALA
MLE
Query on MLE		C [auth F]L-PEPTIDE LINKINGC7 H15 N O2LEU
ORN
Query on ORN		C [auth F]L-PEPTIDE LINKINGC5 H12 N2 O2ALA
ZCL
Query on ZCL		C [auth F]L-PEPTIDE LINKINGC9 H9 Cl2 N O2PHE
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.59 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.221 
  • Space Group: I 21 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 164.331α = 90
b = 164.331β = 90
c = 164.331γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data

Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR56 AI117675

Revision History  (Full details and data files)

  • Version 1.0: 2017-10-04
    Type: Initial release
  • Version 1.1: 2017-10-25
    Changes: Database references
  • Version 1.2: 2017-11-08
    Changes: Database references
  • Version 1.3: 2019-12-11
    Changes: Author supporting evidence
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-10-04
    Changes: Data collection, Database references, Refinement description, Structure summary
  • Version 3.0: 2023-11-15
    Changes: Atomic model, Data collection, Derived calculations