1z6j: Difference between revisions

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-[[Image:1z6j.png|left|200px]]
-{{STRUCTURE_1z6j|  PDB=1z6j  |  SCENE=  }}
+==Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor==
+<StructureSection load='1z6j' size='340' side='right'caption='[[1z6j]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1z6j]] is a 3 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=1Z6J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z6J 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&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PY3:5-[AMINO(IMINO)METHYL]-2-[({[6-[3-AMINO-5-({[(1R)-1-METHYLPROPYL]AMINO}CARBONYL)PHENYL]-3-(ISOPROPYLAMINO)-2-OXOPYRAZIN-1(2H)-YL]ACETYL}AMINO)METHYL]-N-PYRIDIN-4-YLBENZAMIDE'>PY3</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=1z6j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z6j OCA], [https://pdbe.org/1z6j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z6j RCSB], [https://www.ebi.ac.uk/pdbsum/1z6j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z6j 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.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/z6/1z6j_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1z6j ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.
-===Crystal Structure of a ternary complex of Factor VIIa/Tissue Factor/Pyrazinone Inhibitor===
+Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa.,Schweitzer BA, Neumann WL, Rahman HK, Kusturin CL, Sample KR, Poda GI, Kurumbail RG, Stevens AM, Stegeman RA, Stallings WC, South MS Bioorg Med Chem Lett. 2005 Jun 15;15(12):3006-11. PMID:15913999<ref>PMID:15913999</ref>
-{{ABSTRACT_PUBMED_15913999}}
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-==About this Structure==
+<div class="pdbe-citations 1z6j" style="background-color:#fffaf0;"></div>
-[[1z6j]] is a 3 chain structure of [[Factor VIIa]] 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=1Z6J OCA].
 ==See Also==
-*[[Factor VIIa|Factor VIIa]]
+*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
+*[[Tissue factor|Tissue factor]]
-==Reference==
+== References ==
-<ref group="xtra">PMID:015913999</ref><ref group="xtra">PMID:012824026</ref><ref group="xtra">PMID:012954057</ref><references group="xtra"/>
+<references/>
-[[Category: Coagulation factor VIIa]]
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Kurumbail, R G.]]
+[[Category: Large Structures]]
-[[Category: Kusturin, C L.]]
+[[Category: Kurumbail RG]]
-[[Category: Neumann, W L.]]
+[[Category: Kusturin CL]]
-[[Category: Poda, G I.]]
+[[Category: Neumann WL]]
-[[Category: Rahman, H K.]]
+[[Category: Poda GI]]
-[[Category: Sample, K R.]]
+[[Category: Rahman HK]]
-[[Category: Schweitzer, B A.]]
+[[Category: Sample KR]]
-[[Category: Stallings, W C.]]
+[[Category: Schweitzer BA]]
-[[Category: Stegeman, R A.]]
+[[Category: Stallings WC]]
-[[Category: Stevens, A M.]]
+[[Category: Stegeman RA]]
-[[Category: Benzamidine]]
+[[Category: Stevens AM]]
-[[Category: Blood coagulation]]
-[[Category: Cofactor]]
-[[Category: Enzyme inhibitor complex]]
-[[Category: Gla]]
-[[Category: Hydrolase]]
-[[Category: Pyrazinone]]
-[[Category: Serine protease]]
-[[Category: Thrombosis]]
-[[Category: Tissue factor]]