4yt7: Difference between revisions

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-'''Unreleased structure'''
-The entry 4yt7 is ON HOLD  until Paper Publication
+==Factor VIIa in complex with the inhibitor 2-(2-{(R)-[(4-carbamimidoylphenyl)amino][5-ethoxy-2-fluoro-3-(propan-2-yloxy)phenyl]methyl}-1H-imidazol-4-yl)benzamide==
+<StructureSection load='4yt7' size='340' side='right'caption='[[4yt7]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4yt7]] 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=4YT7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YT7 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]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4K1:2-[2-[(R)-[(4-CARBAMIMIDOYLPHENYL)AMINO]-(5-ETHOXY-2-FLUORANYL-3-PROPAN-2-YLOXY-PHENYL)METHYL]-1H-IMIDAZOL-4-YL]BENZAMIDE'>4K1</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=4yt7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yt7 OCA], [https://pdbe.org/4yt7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yt7 RCSB], [https://www.ebi.ac.uk/pdbsum/4yt7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yt7 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.
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Heterocyclic amide isosteres were incorporated into a phenylglycine-based tissue factor/factor VIIa (TF-FVIIa) inhibitor chemotype, providing potent inhibitors. An X-ray co-crystal structure of phenylimidazole 19 suggested that an imidazole nitrogen atom effectively mimics an amide carbonyl, while the phenyl ring forms key hydrophobic interactions with the S1' pocket. Exploration of phenylimidazole substitution led to the discovery of potent, selective and efficacious inhibitors of TF-FVIIa.
-Authors: Wei, A.
+Design and synthesis of potent, selective phenylimidazole-based FVIIa inhibitors.,Glunz PW, Cheng X, Cheney DL, Weigelt CA, Wei A, Luettgen JM, Wong PC, Wexler RR, Priestley ES Bioorg Med Chem Lett. 2015 Mar 30. pii: S0960-894X(15)00268-1. doi:, 10.1016/j.bmcl.2015.03.062. PMID:25881820<ref>PMID:25881820</ref>
-Description: Factor VIIa in complex with the inhibitor 2-(2-{(R)-[(4-carbamimidoylphenyl)amino][5-ethoxy-2-fluoro-3-(propan-2-yloxy)phenyl]methyl}-1H-imidazol-4-yl)benzamide
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Wei, A]]
+<div class="pdbe-citations 4yt7" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Wei A]]