1TZH

Crystal Structure of the Fab YADS1 Complexed with h-VEGF


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Synthetic antibodies from a four-amino-acid code: A dominant role for tyrosine in antigen recognition

Fellouse, F.A.Wiesmann, C.Sidhu, S.S.

(2004) Proc Natl Acad Sci U S A 101: 12467-12472

  • DOI: https://doi.org/10.1073/pnas.0401786101
  • Primary Citation of Related Structures:  
    1TZH, 1TZI

  • PubMed Abstract: 

    Antigen-binding fragments (Fabs) with synthetic antigen-binding sites were isolated from phage-displayed libraries with restricted complementarity-determining region (CDR) diversity. Libraries were constructed such that solvent-accessible CDR positions were randomized with a degenerate codon that encoded for only four amino acids (tyrosine, alanine, aspartate, and serine). Nonetheless, high-affinity Fabs (K(d) = 2-10 nM) were isolated against human vascular endothelial growth factor (hVEGF), and the crystal structures were determined for two distinct Fab-hVEGF complexes. The structures revealed that antigen recognition was mediated primarily by tyrosine side chains, which accounted for 71% of the Fab surface area that became buried upon binding to hVEGF. In contrast, aspartate residues within the CDRs were almost entirely excluded from the binding interface. Alanine and serine residues did not make many direct contacts with antigen, but they allowed for space and conformational flexibility and thus played an auxiliary role in facilitating productive contacts between tyrosine and antigen. Tyrosine side chains were capable of mediating most of the contacts necessary for high-affinity antigen recognition, and, thus, it seems likely that the overabundance of tyrosine in natural antigen-binding sites is a consequence of the side chain being particularly well suited for making productive contacts with antigen. The findings shed light on the basic principles governing the evolution of natural immune repertoires and should also aid the development of improved synthetic antibody libraries.


  • Organizational Affiliation

    Department of Protein Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vascular endothelial growth factor AA [auth V],
B [auth W]
102Homo sapiensMutation(s): 0 
Gene Names: VEGFVEGFA
UniProt & NIH Common Fund Data Resources
Find proteins for P15692 (Homo sapiens)
Explore P15692 
Go to UniProtKB:  P15692
PHAROS:  P15692
GTEx:  ENSG00000112715 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP15692
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Fab YADS1 Light ChainC [auth A],
E [auth L]
213Mus musculusMutation(s): 0 
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Sequence Annotations
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Fab YADS1 Heavy ChainD [auth B],
F [auth H]
229Mus musculusMutation(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: 2.60 Å
  • R-Value Free: 0.271 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.215 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 83.269α = 90
b = 76.269β = 105.77
c = 112.497γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-08-31
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.3: 2023-08-23
    Changes: Data collection, Database references, Refinement description