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3hpt

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'''Unreleased structure'''
 
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The entry 3hpt is ON HOLD
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==Crystal structure of human FxA in complex with (S)-2-cyano-1-(2-methylbenzofuran-5-yl)-3-(2-oxo-1-(2-oxo-2-(pyrrolidin-1-yl)ethyl)azepan-3-yl)guanidine==
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<StructureSection load='3hpt' size='340' side='right'caption='[[3hpt]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3hpt]] 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=3HPT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HPT FirstGlance]. <br>
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</td></tr><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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=YET:1-CYANO-2-(2-METHYL-1-BENZOFURAN-5-YL)-3-[(3S)-2-OXO-1-(2-OXO-2-PYRROLIDIN-1-YLETHYL)AZEPAN-3-YL]GUANIDINE'>YET</scene></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_Xa Coagulation factor Xa], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] </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=3hpt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hpt OCA], [https://pdbe.org/3hpt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hpt RCSB], [https://www.ebi.ac.uk/pdbsum/3hpt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hpt 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/hp/3hpt_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=3hpt 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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The N,N'-disubstituted cyanoguanidine is an excellent bioisostere of the thiourea and ketene aminal functional groups. We report the design and synthesis of a novel class of cyanoguanidine-based lactam derivatives as potent and orally active FXa inhibitors. The SAR studies led to the discovery of compound 4 (BMS-269223, K(i)=6.5nM, EC(2xPT)=32muM) as a selective, orally bioavailable FXa inhibitor with an excellent in vitro liability profile, favorable pharmacokinetics and pharmacodynamics in animal models. The X-ray crystal structure of 4 bound in FXa is presented and key ligand-protein interactions are discussed.
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Authors: Klei, H.E., Ghosh, K., Rushith, A., Kish, K.
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Cyanoguanidine-based lactam derivatives as a novel class of orally bioavailable factor Xa inhibitors.,Shi Y, Zhang J, Shi M, O'Connor SP, Bisaha SN, Li C, Sitkoff D, Pudzianowski AT, Chong S, Klei HE, Kish K, Yanchunas J Jr, Liu EC, Hartl KS, Seiler SM, Steinbacher TE, Schumacher WA, Atwal KS, Stein PD Bioorg Med Chem Lett. 2009 Aug 1;19(15):4034-41. Epub 2009 Jun 13. PMID:19541481<ref>PMID:19541481</ref>
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Description: CRYSTAL STRUCTURE OF HUMAN FXA IN COMPLEX WITH (S)-2-CYANO-1-(2-METHYLBENZOFURAN-5-YL)-3-(2-OXO-1-(2-OXO-2-(PYRROLIDIN-1-YL)ETHYL)AZEPAN-3-YL)GUANIDINE
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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 3hpt" style="background-color:#fffaf0;"></div>
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 17 09:47:42 2009''
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==See Also==
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*[[Factor Xa|Factor Xa]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Coagulation factor Xa]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Ghosh, K]]
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[[Category: Kish, K]]
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[[Category: Klei, H E]]
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[[Category: Rushith, A]]
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[[Category: Blood clotting]]
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[[Category: Blood coagulation]]
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[[Category: Blood coagulation factor]]
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[[Category: Cleavage on pair of basic residue]]
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[[Category: Disulfide bond]]
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[[Category: Egf-like domain]]
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[[Category: Epidermal growth factor like domain]]
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[[Category: Gamma-carboxyglutamic acid]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Hydroxylation]]
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[[Category: Protease]]
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[[Category: Secreted]]
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[[Category: Serine protease]]
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[[Category: Zymogen]]

Current revision

Crystal structure of human FxA in complex with (S)-2-cyano-1-(2-methylbenzofuran-5-yl)-3-(2-oxo-1-(2-oxo-2-(pyrrolidin-1-yl)ethyl)azepan-3-yl)guanidine

PDB ID 3hpt

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