6A76
Crystal structure of the Fab fragment of B5209B, a murine monoclonal antibody specific for the fifth immunoglobulin domain (Ig5) of human ROBO1
Summary for 6A76
| Entry DOI | 10.2210/pdb6a76/pdb |
| Descriptor | Light chain of the anti-human Robo1 antibody B5209B Fab, Heavy chain of the anti-human Robo1 antibody B5209B Fab, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | hepatocellular carcinoma antigen, angiogenesis, immune system, antibody drug |
| Biological source | Mus musculus More |
| Total number of polymer chains | 2 |
| Total formula weight | 47246.35 |
| Authors | Mizohata, E.,Nakayama, T.,Kado, Y.,Inoue, T. (deposition date: 2018-07-02, release date: 2019-01-30, Last modification date: 2024-10-09) |
| Primary citation | Yamashita, T.,Mizohata, E.,Nagatoishi, S.,Watanabe, T.,Nakakido, M.,Iwanari, H.,Mochizuki, Y.,Nakayama, T.,Kado, Y.,Yokota, Y.,Matsumura, H.,Kawamura, T.,Kodama, T.,Hamakubo, T.,Inoue, T.,Fujitani, H.,Tsumoto, K. Affinity Improvement of a Cancer-Targeted Antibody through Alanine-Induced Adjustment of Antigen-Antibody Interface. Structure, 27:519-, 2019 Cited by PubMed Abstract: To investigate favorable single amino acid substitutions that improve antigen-antibody interactions, alanine (Ala) mutagenesis scanning of the interfacial residues of a cancer-targeted antibody, B5209B, was performed based on X-ray crystallography analysis. Two substitutions were shown to significantly enhance the binding affinity for the antigen, by up to 30-fold. One substitution improved the affinity by a gain of binding enthalpy, whereas the other substitution improved the affinity by a gain of binding entropy. Molecular dynamics simulations showed that the enthalpic improvement could be attributed to the stabilization of distant salt bridges located at the periphery of the antigen-antibody interface. The entropic improvement was due to the release of water molecules that were stably trapped in the antigen-antibody interface of the wild-type antibody. Importantly, these effects of the Ala substitutions were caused by subtle adjustments of the binding interface. These results will be helpful to design high-affinity antibodies with avoiding entropy-enthalpy compensation. PubMed: 30595454DOI: 10.1016/j.str.2018.11.002 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.5 Å) |
Structure validation
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