3m36

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{{Seed}}
 
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[[Image:3m36.jpg|left|200px]]
 
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==Factor XA in complex with the inhibitor 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)biphenyl-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423)==
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The line below this paragraph, containing "STRUCTURE_3m36", creates the "Structure Box" on the page.
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<StructureSection load='3m36' size='340' side='right' caption='[[3m36]], [[Resolution|resolution]] 2.15&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'>[[3m36]] is a 2 chain structure with sequence 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=3M36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3M36 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"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=M35:1-[3-(AMINOMETHYL)PHENYL]-N-[3-FLUORO-2-(METHYLSULFONYL)BIPHENYL-4-YL]-3-(TRIFLUOROMETHYL)-1H-PYRAZOLE-5-CARBOXAMIDE'>M35</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3m35|3m35]], [[3m37|3m37]]</td></tr>
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{{STRUCTURE_3m36| PDB=3m36 | SCENE= }}
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3m36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3m36 OCA], [http://pdbe.org/3m36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3m36 RCSB], [http://www.ebi.ac.uk/pdbsum/3m36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3m36 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/FA10_HUMAN FA10_HUMAN]] Defects in F10 are the cause of factor X deficiency (FA10D) [MIM:[http://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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[[http://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/m3/3m36_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=3m36 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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Factor Xa, a serine protease, is at the critical juncture between the intrinsic and extrinsic pathways of the coagulation cascade. Inhibition of factor Xa has the potential to provide effective treatment for both venous and arterial thrombosis. We recently described a series of meta-substituted phenylpyrazoles that are highly potent, selective, and orally bioavailable factor Xa inhibitors. In this paper we report our efforts to further optimize the selectivity profile of our factor Xa inhibitors with a series of ortho- and/or para-substituted phenylpyrazole derivatives. The most potent compounds display sub-nanomolar inhibition constants for factor Xa and show greater than 1000-fold selectivity against other serine proteases. These compounds are also effective in a rabbit model of arteriovenous shunt thrombosis. Optimization of this series led to the preclinical development of DPC602, a 2-(aminomethyl)phenylpyrazole analogue, as a highly potent, selective, and orally bioavailable factor Xa inhibitor.
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===Factor XA in complex with the inhibitor 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)biphenyl-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423)===
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Discovery of 1-(2-aminomethylphenyl)-3-trifluoromethyl-N- [3-fluoro-2'-(aminosulfonyl)[1,1'-biphenyl)]-4-yl]-1H-pyrazole-5-carboxyam ide (DPC602), a potent, selective, and orally bioavailable factor Xa inhibitor(1).,Pruitt JR, Pinto DJ, Galemmo RA Jr, Alexander RS, Rossi KA, Wells BL, Drummond S, Bostrom LL, Burdick D, Bruckner R, Chen H, Smallwood A, Wong PC, Wright MR, Bai S, Luettgen JM, Knabb RM, Lam PY, Wexler RR J Med Chem. 2003 Dec 4;46(25):5298-315. PMID:14640539<ref>PMID:14640539</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 3m36" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_14640539}}, 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 14640539 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_14640539}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3M36 is a 2 chains structure with 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=3M36 OCA].
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==Reference==
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<ref group="xtra">PMID:14640539</ref><references group="xtra"/>
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[[Category: Coagulation factor Xa]]
[[Category: Coagulation factor Xa]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Alexander, R S.]]
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[[Category: Alexander, R S]]
[[Category: Blood coagulation]]
[[Category: Blood coagulation]]
[[Category: Blood coagulation factor]]
[[Category: Blood coagulation factor]]
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[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Plasma]]
[[Category: Plasma]]
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[[Category: Polymorphism]]
 
[[Category: Protease]]
[[Category: Protease]]
[[Category: Protein inhibitor complex]]
[[Category: Protein inhibitor complex]]
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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 Wed Apr 21 10:06:09 2010''
 

Current revision

Factor XA in complex with the inhibitor 1-[3-(aminomethyl)phenyl]-N-[3-fluoro-2'-(methylsulfonyl)biphenyl-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423)

3m36, resolution 2.15Å

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