6m3c: Difference between revisions
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==hAPC-h1573 Fab complex== | |||
<StructureSection load='6m3c' size='340' side='right'caption='[[6m3c]], [[Resolution|resolution]] 3.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M3C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M3C 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]] 3.7Å</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=6m3c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m3c OCA], [https://pdbe.org/6m3c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m3c RCSB], [https://www.ebi.ac.uk/pdbsum/6m3c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m3c ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Activated protein C (APC) is a plasma serine protease with antithrombotic and cytoprotective functions. Based on the hypothesis that specific inhibition of APC's anticoagulant but not its cytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal antibodies (mAbs) are tested: A type I active-site binding mAb and a type II mAb binding to an exosite on APC (required for anticoagulant activity) as shown by X-ray crystallography. Both mAbs increase thrombin generation and promote plasma clotting. Type I blocks all APC activities, whereas type II preserves APC's cytoprotective function. In normal monkeys, type I causes many adverse effects including animal death. In contrast, type II is well-tolerated in normal monkeys and shows both acute and prophylactic dose-dependent efficacy in hemophilic monkeys. Our data show that the type II mAb can specifically inhibit APC's anticoagulant function without compromising its cytoprotective function and offers superior therapeutic opportunities for hemophilia. | |||
Targeted inhibition of activated protein C by a non-active-site inhibitory antibody to treat hemophilia.,Zhao XY, Wilmen A, Wang D, Wang X, Bauzon M, Kim JY, Linden L, Li L, Egner U, Marquardt T, Moosmayer D, Tebbe J, Gluck JM, Ellinger P, McLean K, Yuan S, Yegneswaran S, Jiang X, Evans V, Gu JM, Schneider D, Zhu Y, Xu Y, Mallari C, Hesslein A, Wang Y, Schmidt N, Gutberlet K, Ruehl-Fehlert C, Freyberger A, Hermiston T, Patel C, Sim D, Mosnier LO, Laux V Nat Commun. 2020 Jun 12;11(1):2992. doi: 10.1038/s41467-020-16720-9. PMID:32532974<ref>PMID:32532974</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6m3c" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Egner U]] | |||
[[Category: Wang D]] | |||
[[Category: Wang X]] | |||
[[Category: Zhao X]] | |||
Latest revision as of 11:07, 17 October 2024
hAPC-h1573 Fab complexhAPC-h1573 Fab complex
Structural highlights
Publication Abstract from PubMedActivated protein C (APC) is a plasma serine protease with antithrombotic and cytoprotective functions. Based on the hypothesis that specific inhibition of APC's anticoagulant but not its cytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal antibodies (mAbs) are tested: A type I active-site binding mAb and a type II mAb binding to an exosite on APC (required for anticoagulant activity) as shown by X-ray crystallography. Both mAbs increase thrombin generation and promote plasma clotting. Type I blocks all APC activities, whereas type II preserves APC's cytoprotective function. In normal monkeys, type I causes many adverse effects including animal death. In contrast, type II is well-tolerated in normal monkeys and shows both acute and prophylactic dose-dependent efficacy in hemophilic monkeys. Our data show that the type II mAb can specifically inhibit APC's anticoagulant function without compromising its cytoprotective function and offers superior therapeutic opportunities for hemophilia. Targeted inhibition of activated protein C by a non-active-site inhibitory antibody to treat hemophilia.,Zhao XY, Wilmen A, Wang D, Wang X, Bauzon M, Kim JY, Linden L, Li L, Egner U, Marquardt T, Moosmayer D, Tebbe J, Gluck JM, Ellinger P, McLean K, Yuan S, Yegneswaran S, Jiang X, Evans V, Gu JM, Schneider D, Zhu Y, Xu Y, Mallari C, Hesslein A, Wang Y, Schmidt N, Gutberlet K, Ruehl-Fehlert C, Freyberger A, Hermiston T, Patel C, Sim D, Mosnier LO, Laux V Nat Commun. 2020 Jun 12;11(1):2992. doi: 10.1038/s41467-020-16720-9. PMID:32532974[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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