4ZFO

J22.9-xi: chimeric mouse/human antibody against human BCMA (CD269)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma.

Oden, F.Marino, S.F.Brand, J.Scheu, S.Kriegel, C.Olal, D.Takvorian, A.Westermann, J.Yilmaz, B.Hinz, M.Daumke, O.Hopken, U.E.Muller, G.Lipp, M.

(2015) Mol Oncol 9: 1348-1358

  • DOI: https://doi.org/10.1016/j.molonc.2015.03.010
  • Primary Citation of Related Structures:  
    4ZFO

  • PubMed Abstract: 

    Multiple myeloma (MM) is an aggressive incurable plasma cell malignancy with a median life expectancy of less than seven years. Antibody-based therapies have demonstrated substantial clinical benefit for patients with hematological malignancies, particular in B cell Non-Hodgkin's lymphoma. The lack of immunotherapies specifically targeting MM cells led us to develop a human-mouse chimeric antibody directed against the B cell maturation antigen (BCMA), which is almost exclusively expressed on plasma cells and multiple myeloma cells. The high affinity antibody blocks the binding of the native ligands APRIL and BAFF to BCMA. This finding is rationalized by the high resolution crystal structure of the Fab fragment in complex with the extracellular domain of BCMA. Most importantly, the antibody effectively depletes MM cells in vitro and in vivo and substantially prolongs tumor-free survival under therapeutic conditions in a xenograft mouse model. A BCMA-antibody-based therapy is therefore a promising option for the effective treatment of multiple myeloma and autoimmune diseases.


  • Organizational Affiliation

    Max-Delbrück-Center of Molecular Medicine (MDC), Department of Tumor Genetics and Immunogenetics, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. Electronic address: felix.oden@mdc-berlin.de.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tumor necrosis factor receptor superfamily member 17A [auth F],
F [auth K]
54Homo sapiensMutation(s): 0 
Gene Names: TNFRSF17BCMBCMA
UniProt & NIH Common Fund Data Resources
Find proteins for Q02223 (Homo sapiens)
Explore Q02223 
Go to UniProtKB:  Q02223
PHAROS:  Q02223
GTEx:  ENSG00000048462 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02223
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
J22.9-xi Fab, Light ChainB [auth L]214Mus musculusMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
J22.9-xi Fab, Heavy ChainC [auth H],
E [auth A]
221Mus musculusMutation(s): 0 
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  • Reference Sequence
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Entity ID: 4
MoleculeChains Sequence LengthOrganismDetailsImage
J22.9-xi Fab, Light ChainD [auth B]213Mus 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: 1.90 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.178 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.801α = 90
b = 110.139β = 90
c = 137.279γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PHASERphasing
XDSdata reduction

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
HFSPOGermany--

Revision History  (Full details and data files)

  • Version 1.0: 2015-05-20
    Type: Initial release
  • Version 1.1: 2015-08-12
    Changes: Database references
  • Version 1.2: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Refinement description