7qot

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'''Unreleased structure'''
 
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The entry 7qot is ON HOLD
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==Factor XI and Plasma Kallikrein apple domain structures reveals different kininogen bound complexes==
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<StructureSection load='7qot' size='340' side='right'caption='[[7qot]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7qot]] 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=7QOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QOT FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.24&#8491;</td></tr>
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<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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7qot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qot OCA], [https://pdbe.org/7qot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qot RCSB], [https://www.ebi.ac.uk/pdbsum/7qot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qot ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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BACKGROUND: Plasma prekallikrein (PK) and Factor XI (FXI) are apple domain containing serine proteases which when activated to PKa and FXIa cleave substrates kininogen, Factor XII and Factor IX respectively directing plasma coagulation, bradykinin release, inflammation and thrombosis pathways. OBJECTIVE: To investigate the three-dimensional structure of full-length PKa and perform a comparison with FXI. METHODS: A series of recombinant full-length PKa and FXI constructs and variants were developed and the crystal structures determined. RESULTS AND CONCLUSIONS: A 1.3 A structure of full-length PKa reveals the protease domain positioned above a disc-shaped assemblage of four apple domains in an active conformation. A comparison with the homologous FXI structure reveals the intramolecular disulphide and structural differences in the apple 4 domain that prevents dimer formation in PKa as opposed to FXI. Two latch-like loops (LL1 and LL2) extend from the PKa protease domain to form interactions with the apple 1 and apple 3 domains respectively. A major unexpected difference in the PKa structure compared to FXI is the 180 masculine disc rotation of the apple domains relative to the protease domain. This results in a switched configuration of the latch loops such that LL2 interacts and buries portions of the apple 3 domain in the FXI zymogen whereas in PKa LL2 interacts with the apple 1 domain. Hydrogen-deuterium exchange mass spectrometry on plasma purified human PK and PKa determined that regions of the apple 3 domain have increased surface exposure in PKa compared to the zymogen PK suggesting conformational change upon activation. This article is protected by copyright. All rights reserved.
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Authors: Li, C., Awital, B., Wong, S., Dreveny, I., Meijers, J., Emsley, J.
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Plasma Kallikrein Structure Reveals Apple Domain Disc Rotated Conformation Compared to Factor XI.,Li C, Voos KM, Pathak M, Hall G, McCrae KR, Dreveny I, Li R, Emsley J J Thromb Haemost. 2019 Feb 23. doi: 10.1111/jth.14418. PMID:30801944<ref>PMID:30801944</ref>
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Description: Factor XI and Plasma Kallikrein apple domain structures reveals different kininogen bound complexes
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Dreveny, I]]
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<div class="pdbe-citations 7qot" style="background-color:#fffaf0;"></div>
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[[Category: Li, C]]
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[[Category: Meijers, J]]
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==See Also==
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[[Category: Wong, S]]
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*[[Factor XIa 3D structures|Factor XIa 3D structures]]
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[[Category: Emsley, J]]
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== References ==
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[[Category: Awital, B]]
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Awital B]]
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[[Category: Dreveny I]]
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[[Category: Emsley J]]
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[[Category: Li C]]
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[[Category: Meijers J]]
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[[Category: Wong S]]

Current revision

Factor XI and Plasma Kallikrein apple domain structures reveals different kininogen bound complexes

PDB ID 7qot

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