4EEF

Crystal structure of the designed inhibitor protein F-HB80.4 in complex with the 1918 influenza virus hemagglutinin.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Optimization of affinity, specificity and function of designed influenza inhibitors using deep sequencing.

Whitehead, T.A.Chevalier, A.Song, Y.Dreyfus, C.Fleishman, S.J.De Mattos, C.Myers, C.A.Kamisetty, H.Blair, P.Wilson, I.A.Baker, D.

(2012) Nat Biotechnol 30: 543-548

  • DOI: https://doi.org/10.1038/nbt.2214
  • Primary Citation of Related Structures:  
    4EEF

  • PubMed Abstract: 

    We show that comprehensive sequence-function maps obtained by deep sequencing can be used to reprogram interaction specificity and to leapfrog over bottlenecks in affinity maturation by combining many individually small contributions not detectable in conventional approaches. We use this approach to optimize two computationally designed inhibitors against H1N1 influenza hemagglutinin and, in both cases, obtain variants with subnanomolar binding affinity. The most potent of these, a 51-residue protein, is broadly cross-reactive against all influenza group 1 hemagglutinins, including human H2, and neutralizes H1N1 viruses with a potency that rivals that of several human monoclonal antibodies, demonstrating that computational design followed by comprehensive energy landscape mapping can generate proteins with potential therapeutic utility.


  • Organizational Affiliation

    Department of Biochemistry, University of Washington, Seattle, Washington, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA1 chain
A, C, E
331Influenza A virus (A/Brevig Mission/1/1918(H1N1))Mutation(s): 0 
Gene Names: HAhemagglutinin
UniProt
Find proteins for Q9WFX3 (Influenza A virus (strain A/Brevig Mission/1/1918 H1N1))
Explore Q9WFX3 
Go to UniProtKB:  Q9WFX3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9WFX3
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin HA2 chain
B, D, F
179Influenza A virus (A/Brevig Mission/1/1918(H1N1))Mutation(s): 0 
Gene Names: HAhemagglutinin
UniProt
Find proteins for Q9WFX3 (Influenza A virus (strain A/Brevig Mission/1/1918 H1N1))
Explore Q9WFX3 
Go to UniProtKB:  Q9WFX3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9WFX3
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
F-HB80.4, DESIGNED HEMAGGLUTININ BINDING PROTEIN
G, H, I
74synthetic 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
beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
J, K, L
3N-Glycosylation
Glycosylation Resources
GlyTouCan:  G15407YE
GlyCosmos:  G15407YE
GlyGen:  G15407YE
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.333α = 90
b = 126.151β = 90
c = 243.29γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
XPREPdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-06-27
    Type: Initial release
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Structure summary