7dc7

Crystal structure of D12 Fab-ATP complexCrystal structure of D12 Fab-ATP complex

Structural highlights

7dc7 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 1.77Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

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.

Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment.,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 Cell Rep. 2020 Dec 22;33(12):108542. doi: 10.1016/j.celrep.2020.108542. PMID:33357423^[1]

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

References

↑ 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. 2020 Dec 22;33(12):108542. PMID:33357423 doi:10.1016/j.celrep.2020.108542

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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. 2020 Dec 22;33(12):108542. PMID:33357423 doi:10.1016/j.celrep.2020.108542

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