6m3b: Difference between revisions
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==hAPC-c25k23 Fab complex== | ==hAPC-c25k23 Fab complex== | ||
<StructureSection load='6m3b' size='340' side='right'caption='[[6m3b]]' scene=''> | <StructureSection load='6m3b' size='340' side='right'caption='[[6m3b]], [[Resolution|resolution]] 2.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6M3B OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6m3b]] is a 4 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=6M3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6M3B FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=6m3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6m3b OCA], [https://pdbe.org/6m3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6m3b RCSB], [https://www.ebi.ac.uk/pdbsum/6m3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6m3b ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN] Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:[https://omim.org/entry/176860 176860]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.<ref>PMID:8560401</ref> <ref>PMID:2437584</ref> <ref>PMID:2602169</ref> <ref>PMID:1868249</ref> <ref>PMID:1347706</ref> <ref>PMID:1511989</ref> <ref>PMID:1301959</ref> <ref>PMID:8499568</ref> <ref>PMID:8292730</ref> <ref>PMID:8398832</ref> <ref>PMID:7865674</ref> <ref>PMID:7792728</ref> <ref>PMID:8829639</ref> <ref>PMID:9798967</ref> Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:[https://omim.org/entry/612304 612304]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PROC_HUMAN PROC_HUMAN] Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids. | |||
<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> | |||
</div> | |||
<div class="pdbe-citations 6m3b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Egner U]] | [[Category: Egner U]] | ||