2fzz

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{{Seed}}
 
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[[Image:2fzz.png|left|200px]]
 
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==Factor Xa in complex with the inhibitor 1-(3-amino-1,2-benzisoxazol-5-yl)-6-(2'-(((3r)-3-hydroxy-1-pyrrolidinyl)methyl)-4-biphenylyl)-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7h-pyrazolo[3,4-c]pyridin-7-one==
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The line below this paragraph, containing "STRUCTURE_2fzz", creates the "Structure Box" on the page.
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<StructureSection load='2fzz' size='340' side='right'caption='[[2fzz]], [[Resolution|resolution]] 2.20&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'>[[2fzz]] is a 2 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=2FZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FZZ FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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=5QC:1-(3-AMINO-1,2-BENZISOXAZOL-5-YL)-6-(2-{[(3R)-3-HYDROXYPYRROLIDIN-1-YL]METHYL}BIPHENYL-4-YL)-3-(TRIFLUOROMETHYL)-1,4,5,6-TETRAHYDRO-7H-PYRAZOLO[3,4-C]PYRIDIN-7-ONE'>5QC</scene></td></tr>
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{{STRUCTURE_2fzz| PDB=2fzz | 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=2fzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fzz OCA], [https://pdbe.org/2fzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fzz RCSB], [https://www.ebi.ac.uk/pdbsum/2fzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fzz 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/fz/2fzz_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=2fzz 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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Attempts to further optimize the pyrazole factor Xa inhibitors centered on masking the aryl aniline P4 moiety. Scaffold optimization resulted in the identification of a novel bicyclic pyrazolo-pyridinone scaffold which retained fXa potency. The novel bicyclic scaffold preserved all binding interactions observed with the monocyclic counterpart and importantly the carboxamido moiety was integrated within the scaffold making it less susceptible to hydrolysis. These efforts led to the identification of 1-[3-aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyr rolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-py ridin-7-one 6f (BMS-740808), a highly potent (fXa Ki=30 pM) with a rapid onset of inhibition (2.7x10(7) M-1 s-1) in vitro, selective (&gt;1000-fold over other proteases), efficacious in the AVShunt thrombosis model, and orally bioavailable inhibitor of blood coagulation factor Xa.
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===Factor Xa in complex with the inhibitor 1-(3-amino-1,2-benzisoxazol-5-yl)-6-(2'-(((3r)-3-hydroxy-1-pyrrolidinyl)methyl)-4-biphenylyl)-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7h-pyrazolo[3,4-c]pyridin-7-one===
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1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyr rolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-py ridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa.,Pinto DJ, Orwat MJ, Quan ML, Han Q, Galemmo RA Jr, Amparo E, Wells B, Ellis C, He MY, Alexander RS, Rossi KA, Smallwood A, Wong PC, Luettgen JM, Rendina AR, Knabb RM, Mersinger L, Kettner C, Bai S, He K, Wexler RR, Lam PY Bioorg Med Chem Lett. 2006 Aug 1;16(15):4141-7. Epub 2006 May 30. PMID:16730984<ref>PMID:16730984</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 2fzz" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_16730984}}, 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 16730984 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16730984}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2FZZ 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=2FZZ OCA].
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==Reference==
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<ref group="xtra">PMID:16730984</ref><references group="xtra"/>
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[[Category: Coagulation factor Xa]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Alexander, R S.]]
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[[Category: Large Structures]]
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[[Category: Blood coagulation factor]]
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[[Category: Alexander RS]]
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[[Category: Calcium-binding]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Plasma]]
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[[Category: Protein inhibitor complex]]
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[[Category: Serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 23:20:35 2009''
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Current revision

Factor Xa in complex with the inhibitor 1-(3-amino-1,2-benzisoxazol-5-yl)-6-(2'-(((3r)-3-hydroxy-1-pyrrolidinyl)methyl)-4-biphenylyl)-3-(trifluoromethyl)-1,4,5,6-tetrahydro-7h-pyrazolo[3,4-c]pyridin-7-one

PDB ID 2fzz

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