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3bg8
From Proteopedia
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| - | {{Seed}} | ||
| - | [[Image:3bg8.jpg|left|200px]] | ||
| - | < | + | ==Crystal structure of Factor XIa in complex with Clavatadine A== |
| - | + | <StructureSection load='3bg8' size='340' side='right'caption='[[3bg8]], [[Resolution|resolution]] 1.60Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | or | + | <table><tr><td colspan='2'>[[3bg8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BG8 FirstGlance]. <br> |
| - | or | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=G0R:N-(4-carbamimidamidobutyl)ethanamide'>G0R</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F11 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |
| - | + | <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> | |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bg8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bg8 OCA], [https://pdbe.org/3bg8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bg8 RCSB], [https://www.ebi.ac.uk/pdbsum/3bg8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bg8 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. | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bg/3bg8_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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=3bg8 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bioassay-guided fractionation of a CH2Cl2/MeOH extract of the sponge Suberea clavata using the serine protease factor XIa to detect antithrombotic activity led to the isolation of the new marine natural products, clavatadines A and B. Clavatadines A and B inhibited factor XIa with IC50's of 1.3 and 27 microM, respectively. A crystal structure of protein-inhibitor (clavatadine A) complex was obtained and revealed interesting selective binding and irreversible inhibition of factor XIa. The cocrystal structure provides guidance for the design and synthesis of future factor XIa inhibitors as antithrombotic agents. | ||
| - | + | Clavatadine A, a natural product with selective recognition and irreversible inhibition of factor XIa.,Buchanan MS, Carroll AR, Wessling D, Jobling M, Avery VM, Davis RA, Feng Y, Xue Y, Oster L, Fex T, Deinum J, Hooper JN, Quinn RJ J Med Chem. 2008 Jun 26;51(12):3583-7. PMID:18510371<ref>PMID:18510371</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3bg8" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| - | + | *[[Factor XIa|Factor XIa]] | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | |
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| - | == | + | |
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[[Category: Coagulation factor XIa]] | [[Category: Coagulation factor XIa]] | ||
| - | [[Category: | + | [[Category: Human]] |
| - | [[Category: Oster, L | + | [[Category: Large Structures]] |
| - | [[Category: Xue, Y | + | [[Category: Oster, L]] |
| + | [[Category: Xue, Y]] | ||
[[Category: Alternative splicing]] | [[Category: Alternative splicing]] | ||
[[Category: Blood coagulation]] | [[Category: Blood coagulation]] | ||
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[[Category: Secreted]] | [[Category: Secreted]] | ||
[[Category: Serine protease]] | [[Category: Serine protease]] | ||
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 10 15:00:18 2008'' | ||
Current revision
Crystal structure of Factor XIa in complex with Clavatadine A
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Categories: Coagulation factor XIa | Human | Large Structures | Oster, L | Xue, Y | Alternative splicing | Blood coagulation | Covalent inhibitor | Disease mutation | Factor xia inhibitor complex | Glycoprotein | Heparin-binding | Hydrolase | Polymorphism | Protease inhibitor | Secreted | Serine protease

