1cvw

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[[Image:1cvw.jpg|left|200px]]
 
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==Crystal structure of active site-inhibited human coagulation factor VIIA (DES-GLA)==
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The line below this paragraph, containing "STRUCTURE_1cvw", creates the "Structure Box" on the page.
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<StructureSection load='1cvw' size='340' side='right'caption='[[1cvw]], [[Resolution|resolution]] 2.28&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1cvw]] 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=1CVW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CVW FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.28&#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=0GE:N-{[5-(DIMETHYLAMINO)NAPHTHALEN-1-YL]SULFONYL}-L-ALPHA-GLUTAMYL-N-[(2S,3S)-6-CARBAMIMIDAMIDO-1-CHLORO-2-HYDROXYHEXAN-3-YL]GLYCINAMIDE'>0GE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
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{{STRUCTURE_1cvw| PDB=1cvw | SCENE= }}
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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=1cvw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1cvw OCA], [https://pdbe.org/1cvw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1cvw RCSB], [https://www.ebi.ac.uk/pdbsum/1cvw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1cvw 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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== 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/cv/1cvw_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/main_output.php?pdb_ID=1cvw ConSurf].
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<div style="clear:both"></div>
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'''CRYSTAL STRUCTURE OF ACTIVE SITE-INHIBITED HUMAN COAGULATION FACTOR VIIA (DES-GLA)'''
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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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==Overview==
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<references/>
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Factor VIIa (FVIIa) is a crucial haemostatic protease consisting of four distinct domains termed the Gla, epidermal growth factor-1 (EGF-1), EGF-2, and protease domains (from N- to C-terminus). The crystal structure of human FVIIa inhibited at the active site with 1, 5-dansyl-Glu-Gly-Arg-chloromethyl ketone and lacking the Gla domain has been solved to a resolution of 2.28 A. The EGF-2 and protease domains were well resolved, whereas no electron density for the EGF-1 domain was observed, suggesting a flexible arrangement or disorder within the crystal. Superposition of the protease domain of the present structure with that previously resolved in the tissue factor (TF)/FVIIai complex revealed that although overall the domain structures are similar, the EGF-2 domain is rotated by 7.5 degrees relative to the protease domain on binding TF. A single cleavage in the protease domain was found, between Arg315 and Lys316 (chymotrypsin numbering 170C-170D) in a FVII-specific insertion loop: this cleavage appeared to be essential for crystallisation. Insertion of the heavy chain N-terminal Ile153 is essentially identical in the two structures, as is the geometry of the active site residues and the inhibitor C-terminal arginine residue. Some differences are seen in the cleaved loop, but changes in TF-contact residues are generally minor. This structure supports the hypothesis that TF binding enables spatial domain arrangements in the flexible FVIIa molecule necessary for procoagulant function and furthermore that active site occupancy induces FVIIa active conformation via N-terminal insertion.
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__TOC__
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</StructureSection>
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==About this Structure==
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1CVW is a [[Single protein]] structure of 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=1CVW OCA].
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==Reference==
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Crystal structure of active site-inhibited human coagulation factor VIIa (des-Gla)., Kemball-Cook G, Johnson DJ, Tuddenham EG, Harlos K, J Struct Biol. 1999 Oct;127(3):213-23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10544046 10544046]
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[[Category: Coagulation factor VIIa]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Harlos, K.]]
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[[Category: Harlos K]]
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[[Category: Johnson, D J.D.]]
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[[Category: Johnson DJD]]
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[[Category: Kemball-Cook, G.]]
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[[Category: Kemball-Cook G]]
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[[Category: Tuddenham, E G.D.]]
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[[Category: Tuddenham EGD]]
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[[Category: Blood coagulation]]
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[[Category: Crystal structure]]
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[[Category: Egf]]
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[[Category: Factor viia]]
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[[Category: Inhibitor]]
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[[Category: Serine protease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:09:56 2008''
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Current revision

Crystal structure of active site-inhibited human coagulation factor VIIA (DES-GLA)

PDB ID 1cvw

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