7dc7: Difference between revisions
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==== | ==Crystal structure of D12 Fab-ATP complex== | ||
<StructureSection load='7dc7' size='340' side='right'caption='[[7dc7]]' scene=''> | <StructureSection load='7dc7' size='340' side='right'caption='[[7dc7]], [[Resolution|resolution]] 1.77Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[7dc7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DC7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DC7 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.77Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7dc7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dc7 OCA], [https://pdbe.org/7dc7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dc7 RCSB], [https://www.ebi.ac.uk/pdbsum/7dc7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dc7 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:33357423</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7dc7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Fukami TA]] | ||
[[Category: Kawauchi H]] | |||
[[Category: Mimoto F]] | |||
[[Category: Tatsumi K]] | |||
[[Category: Torizawa T]] | |||
Latest revision as of 19:30, 29 November 2023
Crystal structure of D12 Fab-ATP complexCrystal structure of D12 Fab-ATP complex
Structural highlights
Publication Abstract from PubMedThe 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. See AlsoReferences
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