2C1P

Fab-fragment of enantioselective antibody complexed with finrozole


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.230 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Crystal Structures of an Enantioselective Fab-Fragment in Free and Complex Forms.

Parkkinen, T.Nevanen, T.K.Koivula, A.Rouvinen, J.

(2006) J Mol Biol 357: 471

  • DOI: https://doi.org/10.1016/j.jmb.2005.12.045
  • Primary Citation of Related Structures:  
    2C1O, 2C1P

  • PubMed Abstract: 

    Enantioselective antibodies can separate the enantiomers of a chiral compound in a highly specific manner. We have recently reported the cloning and applications of a recombinant Fab-fragment, ENA11His, in the enantioseparation of a drug candidate, finrozole, which contains two chiral centers. Here, the crystal structures of this enantioselective antibody Fab-fragment are determined in the absence of the hapten at a resolution of 2.75 A, and in the presence of the hapten at 2.05 A resolution. The conformation of the protein was found to be similar in both free and complex forms. The hapten molecule was tightly bound in a deep cleft between the light and heavy chains of the Fab-fragment. The complex structure also allowed us to describe the molecular basis for enantioselectivity and to deduce the absolute configurations of all the four different stereoisomers (a-d) of finrozole. The ENA11His antibody fragment selectively binds the SR (a) enantiomer from the racemic mixture of a and d-enantiomers, thus allowing separation from the pharmacologically most active RS enantiomer (d). In particular, Asp95 and Asn35 of the H-chain in the ENA11 His antibody seem to provide this specificity through hydrogen bonding.


  • Organizational Affiliation

    Department of Chemistry, University of Joensuu, PO Box 111, FIN-80101 Joensuu, Finland.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
IGK-C PROTEINA,
D [auth L]
218Mus musculusMutation(s): 0 
UniProt
Find proteins for Q58EU8 (Mus musculus)
Explore Q58EU8 
Go to UniProtKB:  Q58EU8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ58EU8
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
IGH-4 PROTEINB,
C [auth H]
217Mus musculusMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FNZ
Query on FNZ

Download Ideal Coordinates CCD File 
E [auth B],
F [auth H]
4-[(1S,2R)-3-(4-FLUOROPHENYL)-2-HYDROXY-1-(1H-1,2,4-TRIAZOL-1-YL)PROPYL]BENZONITRILE
C18 H15 F N4 O
SLJZVZKQYSKYNV-MSOLQXFVSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
FNZ PDBBind:  2C1P Kd: 4000 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.230 
  • R-Value Observed: 0.230 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 70.815α = 90
b = 87.419β = 90
c = 141.684γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-01-25
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2019-07-24
    Changes: Data collection
  • Version 1.4: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description