2h9e

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[[Image:2h9e.png|left|200px]]
 
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{{STRUCTURE_2h9e| PDB=2h9e | SCENE= }}
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==Crystal Structure of FXa/selectide/NAPC2 ternary complex==
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<StructureSection load='2h9e' size='340' side='right'caption='[[2h9e]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2h9e]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ancylostoma_caninum Ancylostoma caninum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H9E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H9E 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]] 2.2&#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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DTY:D-TYROSINE'>DTY</scene>, <scene name='pdbligand=LPD:L-PROLINAMIDE'>LPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2h9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h9e OCA], [https://pdbe.org/2h9e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h9e RCSB], [https://www.ebi.ac.uk/pdbsum/2h9e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h9e ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[https://omim.org/entry/227600 227600]. A hemorrhagic disease with variable presentation. Affected individuals can manifest prolonged nasal and mucosal hemorrhage, menorrhagia, hematuria, and occasionally hemarthrosis. Some patients do not have clinical bleeding diathesis.<ref>PMID:2790181</ref> <ref>PMID:1973167</ref> <ref>PMID:1985698</ref> <ref>PMID:7669671</ref> <ref>PMID:8529633</ref> <ref>PMID:7860069</ref> <ref>PMID:8845463</ref> <ref>PMID:8910490</ref> <ref>PMID:10468877</ref> <ref>PMID:10746568</ref> <ref>PMID:10739379</ref> <ref>PMID:11248282</ref> <ref>PMID:11728527</ref> <ref>PMID:12945883</ref> <ref>PMID:15650540</ref> <ref>PMID:17393015</ref> <ref>PMID:19135706</ref>
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== Function ==
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[https://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN] Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
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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/h9/2h9e_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=2h9e 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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NAPc2, an anticoagulant protein from the hematophagous nematode Ancylostoma caninum evaluated in phase-II/IIa clinical trials, inhibits the extrinsic blood coagulation pathway by a two step mechanism, initially interacting with the hitherto uncharacterized factor Xa exosite involved in macromolecular recognition and subsequently inhibiting factor VIIa (K(i)=8.4 pM) of the factor VIIa/tissue factor complex. NAPc2 is highly flexible, becoming partially ordered and undergoing significant structural changes in the C terminus upon binding to the factor Xa exosite. In the crystal structure of the ternary factor Xa/NAPc2/selectide complex, the binding interface consists of an intermolecular antiparallel beta-sheet formed by the segment of the polypeptide chain consisting of residues 74-80 of NAPc2 with the residues 86-93 of factor Xa that is additional maintained by contacts between the short helical segment (residues 67-73) and a turn (residues 26-29) of NAPc2 with the short C-terminal helix of factor Xa (residues 233-243). This exosite is physiologically highly relevant for the recognition and inhibition of factor X/Xa by macromolecular substrates and provides a structural motif for the development of a new class of inhibitors for the treatment of deep vein thrombosis and angioplasty.
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===Crystal Structure of FXa/selectide/NAPC2 ternary complex===
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Intermolecular interactions and characterization of the novel factor Xa exosite involved in macromolecular recognition and inhibition: crystal structure of human Gla-domainless factor Xa complexed with the anticoagulant protein NAPc2 from the hematophagous nematode Ancylostoma caninum.,Murakami MT, Rios-Steiner J, Weaver SE, Tulinsky A, Geiger JH, Arni RK J Mol Biol. 2007 Feb 16;366(2):602-10. Epub 2006 Nov 14. PMID:17173931<ref>PMID:17173931</ref>
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{{ABSTRACT_PUBMED_17173931}}
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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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==About this Structure==
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<div class="pdbe-citations 2h9e" style="background-color:#fffaf0;"></div>
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[[2h9e]] is a 4 chain structure of [[Factor Xa]] with sequence from [http://en.wikipedia.org/wiki/Ancylostoma_caninum Ancylostoma caninum] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H9E OCA].
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==See Also==
==See Also==
*[[Factor Xa|Factor Xa]]
*[[Factor Xa|Factor Xa]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:017173931</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Ancylostoma caninum]]
[[Category: Ancylostoma caninum]]
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[[Category: Coagulation factor Xa]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Arni, R K.]]
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[[Category: Large Structures]]
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[[Category: Geiger, G.]]
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[[Category: Arni RK]]
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[[Category: Murakami, M T.]]
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[[Category: Geiger G]]
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[[Category: Tulinsky, A.]]
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[[Category: Murakami MT]]
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[[Category: Blood clotting]]
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[[Category: Tulinsky A]]
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[[Category: Factor xa]]
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[[Category: Hydrolase-hydrolase inhibitor complex]]
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[[Category: Napc2]]
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[[Category: Selectide]]
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Current revision

Crystal Structure of FXa/selectide/NAPC2 ternary complex

PDB ID 2h9e

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