This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4k23

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 09:50, 11 August 2016

Structure of anti-uPAR Fab ATN-658

Structural highlights

4k23 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4k24
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

The urokinase plasminogen activator receptor (uPAR) plays a role in tumor progression and has been proposed as a target for the treatment of cancer. We recently described the development of a novel humanized monoclonal antibody that targets uPAR and has anti-tumor activity in multiple xenograft animal tumor models. This antibody, ATN-658, does not inhibit ligand binding (i.e. uPA and vitronectin) to uPAR and its mechanism of action remains unclear. As a first step in understanding the anti-tumor activity of ATN-658, we set out to identify the epitope on uPAR to which ATN-658 binds. Guided by comparisons between primate and human uPAR, epitope mapping studies were performed using several orthogonal techniques. Systematic site directed and alanine scanning mutagenesis identified the region of aa 268-275 of uPAR as the epitope for ATN-658. No known function has previously been attributed to this epitope Structural insights into epitope recognition were obtained from structural studies of the Fab fragment of ATN-658 bound to uPAR. The structure shows that the ATN-658 binds to the DIII domain of uPAR, close to the C-terminus of the receptor, corroborating the epitope mapping results. Intriguingly, when bound to uPAR, the complementarity determining region (CDR) regions of ATN-658 closely mimic the binding regions of the integrin CD11b (alphaM), a previously identified uPAR ligand thought to be involved in leukocyte rolling, migration and complement fixation with no known role in tumor progression of solid tumors. These studies reveal a new functional epitope on uPAR involved in tumor progression and demonstrate a previously unrecognized strategy for the therapeutic targeting of uPAR.

Identification of a New Epitope in uPAR as a Target for the Cancer Therapeutic Monoclonal Antibody ATN-658, a Structural Homolog of the uPAR Binding Integrin CD11b (alphaM).,Xu X, Cai Y, Wei Y, Donate F, Juarez J, Parry G, Chen L, Meehan EJ, Ahn RW, Ugolkov A, Dubrovskyi O, O'Halloran TV, Huang M, Mazar AP PLoS One. 2014 Jan 21;9(1):e85349. doi: 10.1371/journal.pone.0085349. eCollection, 2014 Jan 21. PMID:24465541^[1]

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

References

↑ Xu X, Cai Y, Wei Y, Donate F, Juarez J, Parry G, Chen L, Meehan EJ, Ahn RW, Ugolkov A, Dubrovskyi O, O'Halloran TV, Huang M, Mazar AP. Identification of a New Epitope in uPAR as a Target for the Cancer Therapeutic Monoclonal Antibody ATN-658, a Structural Homolog of the uPAR Binding Integrin CD11b (alphaM). PLoS One. 2014 Jan 21;9(1):e85349. doi: 10.1371/journal.pone.0085349. eCollection, 2014 Jan 21. PMID:24465541 doi:http://dx.doi.org/10.1371/journal.pone.0085349

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4k23"

Categories: Mus musculus | Chen, L | Huang, M | Yuan, C | Immune system

@@ Line 1: / Line 1: @@
 ==Structure of anti-uPAR Fab ATN-658==
 <StructureSection load='4k23' size='340' side='right' caption='[[4k23]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[4k23]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K23 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K23 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k24|4k24]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k23 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k23 RCSB], [http://www.ebi.ac.uk/pdbsum/4k23 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4k23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k23 OCA], [http://pdbe.org/4k23 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k23 RCSB], [http://www.ebi.ac.uk/pdbsum/4k23 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k23 ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 14: / Line 15: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4k23" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4k23

From Proteopedia

Revision as of 09:50, 11 August 2016

Structure of anti-uPAR Fab ATN-658

Structural highlights

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox