View source for 6ay2


==Structure of CathB with covalently linked Compound 28==
<StructureSection load='6ay2' size='340' side='right'caption='[[6ay2]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ay2]] 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=6AY2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AY2 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C1G:N~1~-[(2S)-1-amino-5-(carbamoylamino)pentan-2-yl]-N~1~-[(1R)-1-(thiophen-3-yl)ethyl]cyclobutane-1,1-dicarboxamide'>C1G</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=6ay2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ay2 OCA], [https://pdbe.org/6ay2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ay2 RCSB], [https://www.ebi.ac.uk/pdbsum/6ay2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ay2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CATB_HUMAN CATB_HUMAN] Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Antibody-drug conjugates (ADCs) have become an important therapeutic modality for oncology, with three approved by the FDA and over 60 others in clinical trials. Despite the progress, improvements in ADC therapeutic index are desired. Peptide-based ADC linkers that are cleaved by lysosomal proteases have shown sufficient stability in serum and effective payload-release in targeted cells. If the linker can be preferentially hydrolyzed by tumor-specific proteases, safety margin may improve. However, the use of peptide-based linkers limits our ability to modulate protease specificity. Here we report the structure-guided discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing linker is hydrolyzed predominantly by cathepsin B while the valine-citrulline dipeptide linker is not. ADCs bearing the nonpeptidic linker are as efficacious and stable in vivo as those with the dipeptide linker. Our results strongly support the application of the peptidomimetic linker and present new opportunities for improving the selectivity of ADCs.

Discovery of Peptidomimetic Antibody-Drug Conjugate Linkers with Enhanced Protease Specificity.,Wei B, Gunzner-Toste J, Yao H, Wang T, Wang J, Xu Z, Chen J, Wai J, Nonomiya J, Tsai SP, Chuh J, Kozak KR, Liu Y, Yu SF, Lau J, Li G, Phillips GD, Leipold D, Kamath A, Su D, Xu K, Eigenbrot C, Steinbacher S, Ohri R, Raab H, Staben LR, Zhao G, Flygare JA, Pillow TH, Verma V, Safina B J Med Chem. 2017 Dec 21. doi: 10.1021/acs.jmedchem.7b01430. PMID:29227683<ref>PMID:29227683</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ay2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cathepsin 3D structures|Cathepsin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kiefer JR]]
[[Category: Steinbacher S]]