7DC7
Crystal structure of D12 Fab-ATP complex
Summary for 7DC7
| Entry DOI | 10.2210/pdb7dc7/pdb |
| Descriptor | D12 Fab heavy chain, D12 Fab light chain, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total) |
| Functional Keywords | antibody, complex, fab, immune system |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 2 |
| Total formula weight | 47570.46 |
| Authors | Kawauchi, H.,Fukami, T.A.,Tatsumi, K.,Torizawa, T.,Mimoto, F. (deposition date: 2020-10-23, release date: 2021-01-13, Last modification date: 2024-11-20) |
| Primary citation | Mimoto, F.,Tatsumi, K.,Shimizu, S.,Kadono, S.,Haraya, K.,Nagayasu, M.,Suzuki, Y.,Fujii, E.,Kamimura, M.,Hayasaka, A.,Kawauchi, H.,Ohara, K.,Matsushita, M.,Baba, T.,Susumu, H.,Sakashita, T.,Muraoka, T.,Aso, K.,Katada, H.,Tanaka, E.,Nakagawa, K.,Hasegawa, M.,Ayabe, M.,Yamamoto, T.,Tanba, S.,Ishiguro, T.,Kamikawa, T.,Nambu, T.,Kibayashi, T.,Azuma, Y.,Tomii, Y.,Kato, A.,Ozeki, K.,Murao, N.,Endo, M.,Kikuta, J.,Kamata-Sakurai, M.,Ishii, M.,Hattori, K.,Igawa, T. Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment. Cell Rep, 33:108542-108542, 2020 Cited by PubMed Abstract: The extracellular adenosine triphosphate (ATP) concentration is highly elevated in the tumor microenvironment (TME) and remains tightly regulated in normal tissues. Using phage display technology, we establish a method to identify an antibody that can bind to an antigen only in the presence of ATP. Crystallography analysis reveals that ATP bound in between the antibody-antigen interface serves as a switch for antigen binding. In a transgenic mouse model overexpressing the antigen systemically, the ATP switch antibody binds to the antigen in tumors with minimal binding in normal tissues and plasma and inhibits tumor growth. Thus, we demonstrate that elevated extracellular ATP concentration can be exploited to specifically target the TME, giving therapeutic antibodies the ability to overcome on-target off-tumor toxicity. PubMed: 33357423DOI: 10.1016/j.celrep.2020.108542 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.77 Å) |
Structure validation
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