3R2X

Crystal structure of the de novo designed binding protein HB36.3 in complex the the 1918 influenza virus hemagglutinin


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 

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This is version 2.0 of the entry. See complete history


Literature

Computational design of proteins targeting the conserved stem region of influenza hemagglutinin.

Fleishman, S.J.Whitehead, T.A.Ekiert, D.C.Dreyfus, C.Corn, J.E.Strauch, E.M.Wilson, I.A.Baker, D.

(2011) Science 332: 816-821

  • DOI: https://doi.org/10.1126/science.1202617
  • Primary Citation of Related Structures:  
    3R2X

  • PubMed Abstract: 

    We describe a general computational method for designing proteins that bind a surface patch of interest on a target macromolecule. Favorable interactions between disembodied amino acid residues and the target surface are identified and used to anchor de novo designed interfaces. The method was used to design proteins that bind a conserved surface patch on the stem of the influenza hemagglutinin (HA) from the 1918 H1N1 pandemic virus. After affinity maturation, two of the designed proteins, HB36 and HB80, bind H1 and H5 HAs with low nanomolar affinity. Further, HB80 inhibits the HA fusogenic conformational changes induced at low pH. The crystal structure of HB36 in complex with 1918/H1 HA revealed that the actual binding interface is nearly identical to that in the computational design model. Such designed binding proteins may be useful for both diagnostics and therapeutics.


  • Organizational Affiliation

    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Hemagglutinin331Influenza 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
Hemagglutinin179Influenza 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: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HB36.3, designed hemagglutinin binding protein93synthetic 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
alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
D
4N-Glycosylation
Glycosylation Resources
GlyTouCan:  G81315DD
GlyCosmos:  G81315DD
GlyGen:  G81315DD
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
E [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 0.249 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 130.054α = 90
b = 130.054β = 90
c = 313.735γ = 120
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
XPREPdata reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-05-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Structure summary