6aod
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==FXIa antibody complex== | |
| + | <StructureSection load='6aod' size='340' side='right'caption='[[6aod]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6aod]] is a 3 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=6AOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6AOD 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]] 1.8Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6aod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aod OCA], [https://pdbe.org/6aod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aod RCSB], [https://www.ebi.ac.uk/pdbsum/6aod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aod ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[https://omim.org/entry/612416 612416]; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate.<ref>PMID:2813350</ref> <ref>PMID:1547342</ref> <ref>PMID:7888672</ref> <ref>PMID:7669672</ref> <ref>PMID:9401068</ref> <ref>PMID:9787168</ref> <ref>PMID:10027710</ref> <ref>PMID:10606881</ref> <ref>PMID:11895778</ref> <ref>PMID:15026311</ref> <ref>PMID:15180874</ref> <ref>PMID:15953011</ref> <ref>PMID:16607084</ref> <ref>PMID:18005151</ref> <ref>PMID:21668437</ref> <ref>PMID:21457405</ref> <ref>PMID:22016685</ref> <ref>PMID:22322133</ref> <ref>PMID:21999818</ref> <ref>PMID:22159456</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN] Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Coagulation factor XIa is a candidate target for anticoagulants that better separate antithrombotic efficacy from bleeding risk. We report a co-crystal structure of the FXIa protease domain with DEF, a human monoclonal antibody that blocks FXIa function and prevents thrombosis in animal models without detectable increased bleeding. The light chain of DEF occludes the FXIa S1 subsite and active site, while the heavy chain provides electrostatic interactions with the surface of FXIa. The structure accounts for the specificity of DEF for FXIa over its zymogen and related proteases, its active-site-dependent binding, and its ability to inhibit substrate cleavage. The inactive FXIa protease domain used to obtain the DEF-FXIa crystal structure reversed anticoagulant activity of DEF in plasma and in vivo and the activity of a small-molecule FXIa active-site inhibitor in vitro. DEF and this reversal agent for FXIa active-site inhibitors may help support clinical development of FXIa-targeting anticoagulants. | ||
| - | + | Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa Monoclonal Antibody and a Reversal Agent.,Ely LK, Lolicato M, David T, Lowe K, Kim YC, Samuel D, Bessette P, Garcia JL, Mikita T, Minor DL Jr., Coughlin SR Structure. 2018 Feb 6;26(2):187-198.e4. doi: 10.1016/j.str.2017.12.010. Epub 2018, Jan 11. PMID:29336885<ref>PMID:29336885</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6aod" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Factor XIa 3D structures|Factor XIa 3D structures]] | ||
| + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
| + | *[[3D structures of human antibody|3D structures of human antibody]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lolicato M]] | ||
| + | [[Category: Minor DL]] | ||
Current revision
FXIa antibody complex
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