View source for 5tqf


==Factor VIIa in complex with the inhibitor (11R)-11-[(1-aminoisoquinolin-6-yl)amino]-16-(cyclopropylsulfonyl)-13-methyl-2,13-diazatricyclo[13.3.1.1~6,10~]icosa-1(19),6(20),7,9,15,17-hexaene-3,12-dione==
<StructureSection load='5tqf' size='340' side='right'caption='[[5tqf]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5tqf]] 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=5TQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TQF 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]] 1.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7KR:(11R)-11-[(1-AMINOISOQUINOLIN-6-YL)AMINO]-16-(CYCLOPROPYLSULFONYL)-13-METHYL-2,13-DIAZATRICYCLO[13.3.1.1~6,10~]ICOSA-1(19),6(20),7,9,15,17-HEXAENE-3,12-DIONE'>7KR</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=5tqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tqf OCA], [https://pdbe.org/5tqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tqf RCSB], [https://www.ebi.ac.uk/pdbsum/5tqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tqf 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 ==
Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa Ki was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.

Design and Synthesis of Novel Meta-Linked Phenylglycine Macrocyclic FVIIa Inhibitors.,Richter JM, Cheney DL, Bates JA, Wei A, Luettgen JM, Rendina AR, Harper TM, Narayanan R, Wong PC, Seiffert D, Wexler RR, Priestley ES ACS Med Chem Lett. 2016 Nov 1;8(1):67-72. doi: 10.1021/acsmedchemlett.6b00375., eCollection 2017 Jan 12. PMID:28105277<ref>PMID:28105277</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wei A]]