Crystal structure of humanized 44H10 Fab Version 14Crystal structure of humanized 44H10 Fab Version 14

Structural highlights

9b74 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.48Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding. Using a structure-guided approach, we identify and restore framework residues that directly interact with the antigen or indirectly modulate antigen binding by shaping the antibody paratope and engineer a humanized antibody with affinity, biophysical profile, and molecular binding basis comparable to that of the parental 44H10 mAb. As a humanized molecule, this antibody holds promise as a scaffold for the development of MHC class II-targeting therapeutics and vaccines.

Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.,Kassardjian A, Ivanochko D, Barber B, Jetha A, Julien JP Antibodies (Basel). 2024 Jul 16;13(3):57. doi: 10.3390/antib13030057. PMID:39051333[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Kassardjian A, Ivanochko D, Barber B, Jetha A, Julien JP. Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework. Antibodies (Basel). 2024 Jul 16;13(3):57. PMID:39051333 doi:10.3390/antib13030057

9b74, resolution 2.48Å

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