3d67

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{{Seed}}
 
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[[Image:3d67.png|left|200px]]
 
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==Crystal structure of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) in complex with 2-guanidino-ethyl-mercaptosuccinic acid (GEMSA)==
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The line below this paragraph, containing "STRUCTURE_3d67", creates the "Structure Box" on the page.
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<StructureSection load='3d67' size='340' side='right'caption='[[3d67]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[3d67]] 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=3D67 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D67 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]] 3.4&#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=GEM:(2-GUANIDINOETHYLMERCAPTO)SUCCINIC+ACID'>GEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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{{STRUCTURE_3d67| PDB=3d67 | SCENE= }}
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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=3d67 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d67 OCA], [https://pdbe.org/3d67 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d67 RCSB], [https://www.ebi.ac.uk/pdbsum/3d67 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d67 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/CBPB2_HUMAN CBPB2_HUMAN] Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.<ref>PMID:10574983</ref>
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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/d6/3d67_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3d67 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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Thrombin-activatable fibrinolysis inhibitor (TAFI) is a pro-metallocarboxypeptidase that can be proteolytically activated (TAFIa). TAFIa is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. We studied the intrinsic instability of TAFIa by solving crystal structures of TAFI, a TAFI inhibitor (GEMSA) complex and a quadruple TAFI mutant (70-fold more stable active enzyme). The crystal structures show that TAFIa stability is directly related to the dynamics of a 55-residue segment (residues 296-350) that includes residues of the active site wall. Dynamics of this flap are markedly reduced by the inhibitor GEMSA, a known stabilizer of TAFIa, and stabilizing mutations. Our data provide the structural basis for a model of TAFI auto-regulation: in zymogen TAFI the dynamic flap is stabilized by interactions with the activation peptide. Release of the activation peptide increases dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg302. This represents a novel mechanism of enzyme control that enables TAFI to regulate its activity in plasma in the absence of specific inhibitors.
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===Crystal structure of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) in complex with 2-guanidino-ethyl-mercaptosuccinic acid (GEMSA)===
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Crystal structures of TAFI elucidate the inactivation mechanism of activated TAFI: a novel mechanism for enzyme autoregulation.,Marx PF, Brondijk TH, Plug T, Romijn RA, Hemrika W, Meijers JC, Huizinga EG Blood. 2008 Oct 1;112(7):2803-9. Epub 2008 Jun 17. PMID:18559974<ref>PMID:18559974</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3d67" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18559974}}, adds the Publication Abstract to the page
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*[[Carboxypeptidase 3D structures|Carboxypeptidase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18559974 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18559974}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3D67 is a 3 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D67 OCA].
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==Reference==
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<ref group="xtra">PMID:18559974</ref><references group="xtra"/>
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[[Category: Carboxypeptidase U]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Brondijk, T H.C.]]
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[[Category: Large Structures]]
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[[Category: Huizinga, E G.]]
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[[Category: Brondijk THC]]
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[[Category: Alpha/beta hydrolase fold]]
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[[Category: Huizinga EG]]
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[[Category: Alternative splicing]]
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[[Category: Carboxypeptidase]]
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[[Category: Glycoprotein]]
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[[Category: Metal-binding]]
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[[Category: Metalloprotease]]
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[[Category: Polymorphism]]
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[[Category: Protease]]
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[[Category: Protein-inhibitor complex]]
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[[Category: Secreted]]
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[[Category: Zinc]]
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[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 12:22:23 2009''
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Current revision

Crystal structure of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) in complex with 2-guanidino-ethyl-mercaptosuccinic acid (GEMSA)

PDB ID 3d67

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