1wss

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{{STRUCTURE_1wss| PDB=1wss | SCENE= }}
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==Human Factor Viia-Tissue Factor in Complex with peptide-mimetic inhibitor that has two charged groups in P2 and P4==
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===Human Factor Viia-Tissue Factor in Complex with peprid mimetic inhibitor that has two charge groups in P2 and P4===
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<StructureSection load='1wss' size='340' side='right' caption='[[1wss]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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{{ABSTRACT_PUBMED_16510984}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1wss]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WSS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1WSS FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3CB:N-[(3-CARBOXYBENZYL)SULFONYL]ISOLEUCYL-N~1~-{4-[AMINO(IMINO)METHYL]BENZYL}-5-IMINOORNITHINAMIDE'>3CB</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene><br>
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<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1wqv|1wqv]], [[1dan|1dan]]</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Coagulation_factor_VIIa Coagulation factor VIIa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.21 3.4.21.21] </span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wss FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wss OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1wss RCSB], [http://www.ebi.ac.uk/pdbsum/1wss PDBsum]</span></td></tr>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN]] Defects in F7 are the cause of factor VII deficiency (FA7D) [MIM:[http://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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[[http://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. [[http://www.uniprot.org/uniprot/TF_HUMAN TF_HUMAN]] Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.<ref>PMID:12652293</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ws/1wss_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The crystal structure of human factor VIIa/soluble tissue factor (FVIIa/sTF) in complex with a highly selective peptide-mimetic FVIIa inhibitor which shows 1670-fold selectivity against thrombin inhibition has been solved at 2.6 A resolution. The inhibitor is bound to FVIIa/sTF at the S1, S2 and S3 sites and at the additional S1 subsite. Two charged groups, the amidino group in P2 and the carboxylate group in P4, form ionic interactions with Asp60 and Lys192 of FVIIa, respectively. Structural comparisons between factor VIIa and thrombin show that thrombin has oppositely charged residues, Lys60F and Glu192, in the S2 site and the S1 subsites, respectively. These data suggest that the utilization of the differences of charge distribution in the S2 site and the S1 subsites between FVIIa and thrombin is critical for achieving high selectivity against thrombin inhibition. These results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF.
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==Disease==
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Structure of human factor VIIa/tissue factor in complex with a peptide-mimetic inhibitor: high selectivity against thrombin by introducing two charged groups in P2 and P4.,Kadono S, Sakamoto A, Kikuchi Y, Oh-Eda M, Yabuta N, Koga T, Hattori K, Shiraishi T, Haramura M, Kodama H, Ono Y, Esaki T, Sato H, Watanabe Y, Itoh S, Ohta M, Kozono T Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Feb 1;61(Pt, 2):169-73. Epub 2005 Jan 20. PMID:16510984<ref>PMID:16510984</ref>
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[[http://www.uniprot.org/uniprot/FA7_HUMAN FA7_HUMAN]] Defects in F7 are the cause of factor VII deficiency (FA7D) [MIM:[http://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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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://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. [[http://www.uniprot.org/uniprot/TF_HUMAN TF_HUMAN]] Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited protolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.<ref>PMID:12652293</ref>
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</div>
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==About this Structure==
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[[1wss]] is a 3 chain structure 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=1WSS OCA].
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==See Also==
==See Also==
*[[Factor VIIa|Factor VIIa]]
*[[Factor VIIa|Factor VIIa]]
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*[[Tissue factor|Tissue factor]]
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==Reference==
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== References ==
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<ref group="xtra">PMID:016510984</ref><references group="xtra"/><references/>
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<references/>
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__TOC__
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</StructureSection>
[[Category: Coagulation factor VIIa]]
[[Category: Coagulation factor VIIa]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
[[Category: Esaki, T.]]
[[Category: Esaki, T.]]
[[Category: Haramura, M.]]
[[Category: Haramura, M.]]

Revision as of 06:47, 23 July 2014

Human Factor Viia-Tissue Factor in Complex with peptide-mimetic inhibitor that has two charged groups in P2 and P4

1wss, resolution 2.60Å

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