5opy: Difference between revisions
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New page: '''Unreleased structure''' The entry 5opy is ON HOLD until Paper Publication Authors: Backovic, M., Veesler, D., Borst, A.J., James, Z.M., Zagotta, W., Ginsberg, M., Rey, F.A., DiMaio, ... |
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==Crystal structure of anti-alphaVbeta3 integrin Fab LM609== | |||
<StructureSection load='5opy' size='340' side='right'caption='[[5opy]], [[Resolution|resolution]] 2.26Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5opy]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OPY FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26Å</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=5opy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5opy OCA], [https://pdbe.org/5opy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5opy RCSB], [https://www.ebi.ac.uk/pdbsum/5opy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5opy ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The LM609 antibody specifically recognizes alphaVbeta3 integrin and inhibits angiogenesis, bone resorption, and viral infections in an arginine-glycine-aspartate-independent manner. LM609 entered phase II clinical trials for the treatment of several cancers and was also used for alphaVbeta3-targeted radioimmunotherapy. To elucidate the mechanisms of recognition and inhibition of alphaVbeta3 integrin, we solved the structure of the LM609 antigen-binding fragment by X-ray crystallography and determined its binding affinity for alphaVbeta3. Using single-particle electron microscopy, we show that LM609 binds at the interface between the beta-propeller domain of the alphaV chain and the betaI domain of the beta3 chain, near the RGD-binding site, of all observed integrin conformational states. Integrating these data with fluorescence size-exclusion chromatography, we demonstrate that LM609 sterically hinders access of large ligands to the RGD-binding pocket, without obstructing it. This work provides a structural framework to expedite future efforts utilizing LM609 as a diagnostic or therapeutic tool. | |||
The Therapeutic Antibody LM609 Selectively Inhibits Ligand Binding to Human alphaVbeta3 Integrin via Steric Hindrance.,Borst AJ, James ZM, Zagotta WN, Ginsberg M, Rey FA, DiMaio F, Backovic M, Veesler D Structure. 2017 Oct 7. pii: S0969-2126(17)30298-8. doi:, 10.1016/j.str.2017.09.007. PMID:29033288<ref>PMID:29033288</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5opy" style="background-color:#fffaf0;"></div> | ||
[[Category: Backovic | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Ginsberg | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Rey | [[Category: Mus musculus]] | ||
[[Category: | [[Category: Backovic M]] | ||
[[Category: Borst AJ]] | |||
[[Category: DiMaio F]] | |||
[[Category: Ginsberg M]] | |||
[[Category: James ZM]] | |||
[[Category: Rey FA]] | |||
[[Category: Veesler D]] | |||
[[Category: Zagotta W]] | |||
