View source for 4jyu


==Structure of factor VIIA in complex with the inhibitor (2R)-2-[(1-AMINOISOQUINOLIN-6-YL)AMINO]-2-[3-ETHOXY-4-(PROPAN-2-YLOXY)PHENYL]-N-(PHENYLSULFONYL)ETHANAMIDE==
<StructureSection load='4jyu' size='340' side='right'caption='[[4jyu]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4jyu]] 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=4JYU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JYU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1OK:(2R)-2-[(1-AMINOISOQUINOLIN-6-YL)AMINO]-2-[3-ETHOXY-4-(PROPAN-2-YLOXY)PHENYL]-N-(PHENYLSULFONYL)ETHANAMIDE'>1OK</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4jyu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jyu OCA], [https://pdbe.org/4jyu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jyu RCSB], [https://www.ebi.ac.uk/pdbsum/4jyu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jyu ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN] Defects in F7 are the cause of factor VII deficiency (FA7D) [MIM:[https://omim.org/entry/227500 227500]. A hemorrhagic disease with variable presentation. The clinical picture can be very severe, with the early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, moderate with cutaneous-mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by a surgical intervention. Finally, numerous subjects are completely asymptomatic despite very low factor VII levels.<ref>PMID:8043443</ref> <ref>PMID:2070047</ref> <ref>PMID:1634227</ref> <ref>PMID:8364544</ref> <ref>PMID:8204879</ref> <ref>PMID:7981691</ref> <ref>PMID:7974346</ref> <ref>PMID:8652821</ref> <ref>PMID:8844208</ref> <ref>PMID:8940045</ref> <ref>PMID:8883260</ref> <ref>PMID:9414278</ref> <ref>PMID:9576180</ref> <ref>PMID:9452082</ref> <ref>PMID:11091194</ref> <ref>PMID:11129332</ref> <ref>PMID:10862079</ref> <ref>PMID:12472587</ref> <ref>PMID:14717781</ref> <ref>PMID:19751712</ref> <ref>PMID:18976247</ref> <ref>PMID:19432927</ref> <ref>PMID:21206266</ref> <ref>PMID:21372693</ref> 
== Function ==
[https://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN] Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.
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== Publication Abstract from PubMed ==
Aminoisoquinoline and isoquinoline groups have successfully replaced the more basic P1 benzamidine group of an acylsulfonamide factor VIIa inhibitor. Inhibitory activity was optimized by the identification of additional hydrophobic and hydrophilic P' binding interactions. The molecular details of these interactions were elucidated by X-ray crystallography and molecular modeling. We also show that decreasing the basicity of the P1 group results in improved oral bioavailability in this chemotype.

Nonbenzamidine acylsulfonamide tissue factor-factor VIIa inhibitors.,Glunz PW, Zhang X, Zou Y, Delucca I, Nirschl AH, Cheng X, Weigelt CA, Cheney DL, Wei A, Anumula R, Luettgen JM, Rendina AR, Harpel M, Luo G, Knabb R, Wong PC, Wexler RR, Priestley ES Bioorg Med Chem Lett. 2013 Jun 21. pii: S0960-894X(13)00736-1. doi:, 10.1016/j.bmcl.2013.06.027. PMID:23845220<ref>PMID:23845220</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4jyu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Anumula R]]
[[Category: Wei A]]