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2ra0

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{{Seed}}
 
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[[Image:2ra0.png|left|200px]]
 
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==X-ray Structure of FXa in complex with 7-fluoroindazole==
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The line below this paragraph, containing "STRUCTURE_2ra0", creates the "Structure Box" on the page.
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<StructureSection load='2ra0' size='340' side='right'caption='[[2ra0]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[2ra0]] is a 2 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=2RA0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RA0 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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=JNJ:1-(3-AMINO-1,2-BENZISOXAZOL-5-YL)-6-(4-{2-[(DIMETHYLAMINO)METHYL]-1H-IMIDAZOL-1-YL}-2-FLUOROPHENYL)-7-FLUORO-1H-INDAZOLE-3-CARBOXAMIDE'>JNJ</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F10 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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{{STRUCTURE_2ra0| PDB=2ra0 | SCENE= }}
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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=2ra0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ra0 OCA], [https://pdbe.org/2ra0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ra0 RCSB], [https://www.ebi.ac.uk/pdbsum/2ra0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ra0 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/ra/2ra0_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=2ra0 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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We have developed a novel series of potent and selective factor Xa inhibitors that employ a key 7-fluoroindazolyl moiety. The 7-fluoro group on the indazole scaffold replaces the carbonyl group of an amide that is found in previously reported factor Xa inhibitors. The structure of a factor Xa cocrystal containing 7-fluoroindazole 51a showed the 7-fluoro atom hydrogen-bonding with the N-H of Gly216 (2.9 A) in the peptide backbone. Thus, the 7-fluoroindazolyl moiety not only occupied the same space as the carbonyl group of an amide found in prior factor Xa inhibitors but also maintained a hydrogen bond interaction with the protein's beta-sheet domain. The structure-activity relationship for this series was consistent with this finding, as the factor Xa inhibitory potencies were about 60-fold greater (DeltaDelta G approximately 2.4 kcal/mol) for the 7-fluoroindazoles 25a and 25c versus the corresponding indazoles 25b and 25d. Highly convergent synthesis of these factor Xa inhibitors is also described.
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===X-ray Structure of FXa in complex with 7-fluoroindazole===
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7-fluoroindazoles as potent and selective inhibitors of factor Xa.,Lee YK, Parks DJ, Lu T, Thieu TV, Markotan T, Pan W, McComsey DF, Milkiewicz KL, Crysler CS, Ninan N, Abad MC, Giardino EC, Maryanoff BE, Damiano BP, Player MR J Med Chem. 2008 Jan 24;51(2):282-97. Epub 2007 Dec 27. PMID:18159923<ref>PMID:18159923</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 2ra0" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18159923}}, adds the Publication Abstract to the page
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*[[Factor Xa|Factor Xa]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18159923 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_18159923}}
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__TOC__
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</StructureSection>
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==Disease==
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Known disease associated with this structure: Factor X deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227600 227600]]
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==About this Structure==
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2RA0 is a 2 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=2RA0 OCA].
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==Reference==
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<ref group="xtra">PMID:18159923</ref><references group="xtra"/>
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[[Category: Coagulation factor Xa]]
[[Category: Coagulation factor Xa]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Abad, M C.]]
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[[Category: Large Structures]]
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[[Category: Abad, M C]]
[[Category: Blood coagulation]]
[[Category: Blood coagulation]]
[[Category: Calcium]]
[[Category: Calcium]]
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[[Category: Serine protease]]
[[Category: Serine protease]]
[[Category: Zymogen]]
[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 09:26:31 2009''
 

Current revision

X-ray Structure of FXa in complex with 7-fluoroindazole

PDB ID 2ra0

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