5u6j

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'''Unreleased structure'''
 
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The entry 5u6j is ON HOLD until Paper Publication
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==Factor VIIa in complex with the inhibitor 3-{[(2R)-17-ethyl-4-methyl-3,12-dioxo-7-[(propan-2-yl)sulfonyl]-13-oxa-4,11-diazatricyclo[14.2.2.1~6,10~]henicosa-1(18),6(21),7,9,16,19-hexaen-2-yl]amino}benzamide==
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<StructureSection load='5u6j' size='340' side='right'caption='[[5u6j]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5u6j]] 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=5U6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U6J FirstGlance]. <br>
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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]] 2.3&#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=82J:3-{[(2R)-17-ETHYL-4-METHYL-3,12-DIOXO-7-[(PROPAN-2-YL)SULFONYL]-13-OXA-4,11-DIAZATRICYCLO[14.2.2.1~6,10~]HENICOSA-1(18),6(21),7,9,16,19-HEXAEN-2-YL]AMINO}BENZAMIDE'>82J</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>
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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=5u6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6j OCA], [https://pdbe.org/5u6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u6j RCSB], [https://www.ebi.ac.uk/pdbsum/5u6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6j ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Factor VIIa (FVIIa) inhibitors have shown strong antithrombotic efficacy in preclinical thrombosis models with limited bleeding liabilities. Discovery of potent, orally active FVIIa inhibitors has been largely unsuccessful due to the requirement of a basic P1 group to interact with Asp189 in the S1 binding pocket, limiting their membrane permeability. We have combined recently reported neutral P1 binding substituents with a highly optimized macrocyclic chemotype to produce FVIIa inhibitors with low nanomolar potency and enhanced permeability.
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Authors: Wei, A.
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Neutral macrocyclic factor VIIa inhibitors.,Wurtz NR, Parkhurst BL, DeLucca I, Glunz PW, Jiang W, Zhang X, Cheney DL, Bozarth JM, Rendina AR, Wei A, Harper T, Luettgen JM, Wu Y, Wong PC, Seiffert DA, Wexler RR, Priestley ES Bioorg Med Chem Lett. 2017 Apr 19. pii: S0960-894X(17)30372-4. doi:, 10.1016/j.bmcl.2017.04.008. PMID:28460818<ref>PMID:28460818</ref>
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Description: Factor VIIa in complex with the inhibitor 3-{[(2R)-17-ethyl-4-methyl-3,12-dioxo-7-[(propan-2-yl)sulfonyl]-13-oxa-4,11-diazatricyclo[14.2.2.1~6,10~]henicosa-1(18),6(21),7,9,16,19-hexaen-2-yl]amino}benzamide
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Wei, A]]
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<div class="pdbe-citations 5u6j" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
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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: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Wei A]]

Current revision

Factor VIIa in complex with the inhibitor 3-{[(2R)-17-ethyl-4-methyl-3,12-dioxo-7-[(propan-2-yl)sulfonyl]-13-oxa-4,11-diazatricyclo[14.2.2.1~6,10~]henicosa-1(18),6(21),7,9,16,19-hexaen-2-yl]amino}benzamide

PDB ID 5u6j

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