5GIR

Crystal structure of a Fab fragment with its ligand peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

Structural basis for multi-specific peptide recognition by the anti-IDH1/2 monoclonal antibody, MsMab-1.

Kitago, Y.Kaneko, M.K.Ogasawara, S.Kato, Y.Takagi, J.

(2016) Biochem Biophys Res Commun 478: 1274-1279

  • DOI: https://doi.org/10.1016/j.bbrc.2016.08.110
  • Primary Citation of Related Structures:  
    5GIR, 5GIS

  • PubMed Abstract: 

    A point mutation in isocitrate dehydrogenase 1 (IDH1) and IDH2 is directly linked to the pathogenesis of certain types of tumors. To detect this mutation, several antibodies that can distinguish between mutant and wild-type enzymes have been established. One of which, MsMab-1, has a unique multi-specific character against several types of mutated IDH1/2. This promiscuous character is in remarkable contrast to the highly specific antigen recognition typically observed with a monoclonal antibody. We solved the crystal structure of MsMab-1 Fab fragment in complex with either IDH1 or IDH2-derived peptides. Based on the structure, it became clear that the peptide-binding pocket of the antibody is highly complementary to the core determinant shared between the IDH1 and IDH2, while leaving just enough space for the side chain of the pathogenic but not the wild-type amino acids located in the mutation position. Clarification of the molecular basis for the peculiar binding characteristics of MsMab-1 in atomic detail will help facilitating its diagnostic application, and may be used to develop better diagnostic reagents through structure-guided protein engineering.


  • Organizational Affiliation

    Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chain of Fab fragmentA [auth H],
C [auth A]
240Mus musculusMutation(s): 0 
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Light chain of Fab fragmentB [auth L],
D [auth B]
234Mus musculusMutation(s): 0 
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
LYS-PRO-ILE-ILE-ILE-GLY-SER-HIS-ALA-TYR-GLY-ASPE [auth C],
F [auth D]
12Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O75874 (Homo sapiens)
Explore O75874 
Go to UniProtKB:  O75874
PHAROS:  O75874
GTEx:  ENSG00000138413 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO75874
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SO4
Query on SO4

Download Ideal Coordinates CCD File 
G [auth H]
H
I [auth H]
J [auth L]
K [auth L]
G [auth H],
H,
I [auth H],
J [auth L],
K [auth L],
L,
M [auth A],
N [auth A],
Q [auth B]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
EDO
Query on EDO

Download Ideal Coordinates CCD File 
O [auth A],
P [auth A]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
A [auth H],
C [auth A]
L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.93 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 69.11α = 90
b = 93.65β = 107.51
c = 70.56γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata processing
XDSdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-09-14
    Type: Initial release
  • Version 1.1: 2017-12-06
    Changes: Data collection, Database references, Derived calculations
  • Version 2.0: 2023-11-08
    Changes: Data collection, Database references, Polymer sequence, Refinement description