5VID

Receptor binding domain of BoNT/B in complex with mini-protein binder Bot.0671.2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.75 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Massively parallel de novo protein design for targeted therapeutics.

Chevalier, A.Silva, D.A.Rocklin, G.J.Hicks, D.R.Vergara, R.Murapa, P.Bernard, S.M.Zhang, L.Lam, K.H.Yao, G.Bahl, C.D.Miyashita, S.I.Goreshnik, I.Fuller, J.T.Koday, M.T.Jenkins, C.M.Colvin, T.Carter, L.Bohn, A.Bryan, C.M.Fernandez-Velasco, D.A.Stewart, L.Dong, M.Huang, X.Jin, R.Wilson, I.A.Fuller, D.H.Baker, D.

(2017) Nature 550: 74-79

  • DOI: https://doi.org/10.1038/nature23912
  • Primary Citation of Related Structures:  
    5VID, 5VLI, 5VMR

  • PubMed Abstract: 

    De novo protein design holds promise for creating small stable proteins with shapes customized to bind therapeutic targets. We describe a massively parallel approach for designing, manufacturing and screening mini-protein binders, integrating large-scale computational design, oligonucleotide synthesis, yeast display screening and next-generation sequencing. We designed and tested 22,660 mini-proteins of 37-43 residues that target influenza haemagglutinin and botulinum neurotoxin B, along with 6,286 control sequences to probe contributions to folding and binding, and identified 2,618 high-affinity binders. Comparison of the binding and non-binding design sets, which are two orders of magnitude larger than any previously investigated, enabled the evaluation and improvement of the computational model. Biophysical characterization of a subset of the binder designs showed that they are extremely stable and, unlike antibodies, do not lose activity after exposure to high temperatures. The designs elicit little or no immune response and provide potent prophylactic and therapeutic protection against influenza, even after extensive repeated dosing.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Botulinum neurotoxin type BA [auth D],
B,
C,
D [auth A],
E
438Clostridium botulinumMutation(s): 0 
Gene Names: botB
EC: 3.4.24.69
UniProt
Find proteins for P10844 (Clostridium botulinum)
Explore P10844 
Go to UniProtKB:  P10844
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10844
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Bot.0671.2
F, G, H, I
66unidentifiedMutation(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: 2.75 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 140.887α = 90
b = 87.314β = 114.53
c = 148.455γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-09-20
    Type: Initial release
  • Version 1.1: 2017-10-18
    Changes: Database references
  • Version 1.2: 2023-10-04
    Changes: Data collection, Database references, Refinement description