2j8j

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{{STRUCTURE_2j8j| PDB=2j8j | SCENE= }}
 
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===SOLUTION STRUCTURE OF THE A4 DOMAIN OF BLOOD COAGULATION FACTOR XI===
 
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{{ABSTRACT_PUBMED_17884987}}
 
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==Disease==
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==Solution Structure of the A4 Domain of Blood Coagulation Factor XI==
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[[http://www.uniprot.org/uniprot/FA11_HUMAN FA11_HUMAN]] Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:[http://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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<StructureSection load='2j8j' size='340' side='right'caption='[[2j8j]], [[NMR_Ensembles_of_Models | 14 NMR models]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2j8j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J8J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J8J FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xx9|1xx9]], [[1xxd|1xxd]], [[1xxf|1xxf]], [[1zhm|1zhm]], [[1zhp|1zhp]], [[1zhr|1zhr]], [[1zjd|1zjd]], [[1zlr|1zlr]], [[1zmj|1zmj]], [[1zml|1zml]], [[1zmn|1zmn]], [[1zom|1zom]], [[1zpz|1zpz]], [[1zrk|1zrk]], [[1zsj|1zsj]], [[1zsk|1zsk]], [[1zsl|1zsl]], [[1ztj|1ztj]], [[1ztk|1ztk]], [[1ztl|1ztl]], [[2j8l|2j8l]]</div></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Coagulation_factor_XIa Coagulation factor XIa], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.27 3.4.21.27] </span></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=2j8j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j8j OCA], [https://pdbe.org/2j8j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j8j RCSB], [https://www.ebi.ac.uk/pdbsum/2j8j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j8j 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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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/j8/2j8j_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2j8j ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Factor XI (FXI) is a homodimeric blood coagulation protein. Each monomer comprises four tandem apple-domain repeats (A1-A4) and a serine protease domain. We report here the NMR solution structure of the A4 domain (residues 272-361), which mediates formation of the disulfide-linked FXI dimer. A4 exhibits characteristic features of the plasminogen apple nematode domain family, including a five-stranded beta-sheet flanked by an alpha-helix on one side and a two-stranded beta-sheet on the other. In addition, the solution structure reveals a second alpha-helix at the C terminus. Comparison with a recent crystal structure of full-length FXI, combined with molecular modeling, suggests that the C-terminal helix is formed only upon proteolytic activation. The newly formed helix disrupts interdomain contacts and reorients the catalytic domains, bringing the active sites into close proximity. This hypothesis is supported by small-angle x-ray scattering and electron microscopy data, which indicate that FXI activation is accompanied by a major change in shape. The results are consistent with biochemical evidence that activated FXI cleaves its substrate at two positions without release of an intermediate.
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==Function==
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Solution structure of the A4 domain of factor XI sheds light on the mechanism of zymogen activation.,Samuel D, Cheng H, Riley PW, Canutescu AA, Nagaswami C, Weisel JW, Bu Z, Walsh PN, Roder H Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15693-8. Epub 2007 Sep 20. PMID:17884987<ref>PMID:17884987</ref>
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[[http://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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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[2j8j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J8J OCA].
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</div>
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<div class="pdbe-citations 2j8j" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
*[[Factor XIa|Factor XIa]]
*[[Factor XIa|Factor XIa]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017884987</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Coagulation factor XIa]]
[[Category: Coagulation factor XIa]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Bu, Z.]]
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[[Category: Large Structures]]
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[[Category: Canutescu, A A.]]
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[[Category: Bu, Z]]
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[[Category: Cheng, H.]]
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[[Category: Canutescu, A A]]
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[[Category: Riley, P W.]]
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[[Category: Cheng, H]]
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[[Category: Roder, H.]]
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[[Category: Riley, P W]]
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[[Category: Samuel, D.]]
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[[Category: Roder, H]]
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[[Category: Walsh, P N.]]
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[[Category: Samuel, D]]
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[[Category: Walsh, P N]]
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[[Category: Alternative splicing]]
[[Category: Disease mutation]]
[[Category: Disease mutation]]
[[Category: Fxi / blood coagulation / pan domain /apple domain / blood coagulation]]
[[Category: Fxi / blood coagulation / pan domain /apple domain / blood coagulation]]
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[[Category: Heparin-binding]]
[[Category: Heparin-binding]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
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[[Category: Polymorphism]]
[[Category: Protease]]
[[Category: Protease]]
[[Category: Serine protease]]
[[Category: Serine protease]]

Current revision

Solution Structure of the A4 Domain of Blood Coagulation Factor XI

PDB ID 2j8j

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