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| | <StructureSection load='5jmr' size='340' side='right'caption='[[5jmr]], [[Resolution|resolution]] 2.27Å' scene=''> | | <StructureSection load='5jmr' size='340' side='right'caption='[[5jmr]], [[Resolution|resolution]] 2.27Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jmr]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Arabian_camel Arabian camel]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JMR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JMR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jmr]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Camelus_dromedarius Camelus dromedarius]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JMR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JMR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.27Å</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=5jmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jmr OCA], [http://pdbe.org/5jmr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jmr RCSB], [http://www.ebi.ac.uk/pdbsum/5jmr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jmr ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=5jmr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jmr OCA], [https://pdbe.org/5jmr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jmr RCSB], [https://www.ebi.ac.uk/pdbsum/5jmr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jmr ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arabian camel]] | + | [[Category: Camelus dromedarius]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dahms, S O]] | + | [[Category: Dahms SO]] |
| - | [[Category: Than, M E]] | + | [[Category: Than ME]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Camelid]]
| + | |
| - | [[Category: Furin]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Publication Abstract from PubMed
Proprotein Convertases (PCs) represent highly selective serine proteases that activate their substrates upon proteolytic cleavage. Their inhibition is a promising strategy for the treatment of cancer and infectious diseases. Inhibitory camelid antibodies were developed, targeting the prototypical PC furin. Kinetic analyses of them revealed an enigmatic non-competitive mechanism, affecting the inhibition of large proprotein-like but not small peptidic substrates. Here we present the crystal structures of furin in complex with the antibody Nb14 and of free Nb14 at resolutions of 2.0 A and 2.3 A, respectively. Nb14 binds at a site distant to the substrate binding pocket to the P-domain of furin. Interestingly, no major conformational changes were observed upon complex formation, neither for the protease nor for the antibody. Inhibition of furin by Nb14 is instead explained by steric exclusion of specific substrate conformers, explaining why Nb14 inhibits the processing of bulky protein substrates but not of small peptide substrates. This mode of action was further supported by modelling studies with the ternary factor X-furin-antibody complex and a mutation that disrupted the interaction interface between furin and the antibody. The observed binding mode of Nb14 suggests a novel approach for the development of highly specific antibody-based proprotein convertase inhibitors.
The structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers.,Dahms SO, Creemers JW, Schaub Y, Bourenkov GP, Zogg T, Brandstetter H, Than ME Sci Rep. 2016 Sep 27;6:34303. doi: 10.1038/srep34303. PMID:27670069[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Dahms SO, Creemers JW, Schaub Y, Bourenkov GP, Zogg T, Brandstetter H, Than ME. The structure of a furin-antibody complex explains non-competitive inhibition by steric exclusion of substrate conformers. Sci Rep. 2016 Sep 27;6:34303. doi: 10.1038/srep34303. PMID:27670069 doi:http://dx.doi.org/10.1038/srep34303
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