3ela: Difference between revisions

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-{{Seed}}
-[[Image:3ela.jpg|left|200px]]
-<!--
+==Crystal structure of active site inhibited coagulation factor VIIA mutant in complex with soluble tissue factor==
-The line below this paragraph, containing "STRUCTURE_3ela", creates the "Structure Box" on the page.
+<StructureSection load='3ela' size='340' side='right'caption='[[3ela]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3ela]] 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=3ELA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ELA FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0Z6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PHENYLALANINAMIDE'>0Z6</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene></td></tr>
-{{STRUCTURE_3ela|  PDB=3ela  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ela FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ela OCA], [https://pdbe.org/3ela PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ela RCSB], [https://www.ebi.ac.uk/pdbsum/3ela PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ela 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/el/3ela_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3ela ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The intrinsic activity of coagulation factor VIIa (FVIIa) is dependent on Ca(2+) binding to a loop (residues 210-220) in the protease domain. Structural analysis revealed that Ca(2+) may enhance the activity by attenuating electrostatic repulsion of Glu(296) and/or by facilitating interactions between the loop and Lys(161) in the N-terminal tail. In support of the first mechanism, the mutations E296V and D212N resulted in similar, about 2-fold, enhancements of the amidolytic activity. Moreover, mutation of the Lys(161)-interactive residue Asp(217) or Asp(219) to Ala reduced the amidolytic activity by 40-50%, whereas the K161A mutation resulted in 80% reduction. Hence one of these Asp residues in the Ca(2+)-binding loop appears to suffice for some residual interaction with Lys(161), whereas the more severe effect upon replacement of Lys(161) is due to abrogation of the interaction with the N-terminal tail. However, Ca(2+) attenuation of the repulsion between Asp(212) and Glu(296) keeps the activity above that of apoFVIIa. Altogether, our data suggest that repulsion involving Asp(212) in the Ca(2+)-binding loop suppresses FVIIa activity and that optimal activity requires a favorable interaction between the Ca(2+)-binding loop and the N-terminal tail. Crystal structures of tissue factor-bound FVIIa(D212N) and FVIIa(V158D/E296V/M298Q) revealed altered hydrogen bond networks, resembling those in factor Xa and thrombin, after introduction of the D212N and E296V mutations plausibly responsible for tethering the N-terminal tail to the activation domain. The charge repulsion between the Ca(2+)-binding loop and the activation domain appeared to be either relieved by charge removal and new hydrogen bonds (D212N) or abolished (E296V). We propose that Ca(2+) stimulates the intrinsic FVIIa activity by a combination of charge neutralization and loop stabilization.
-===Crystal structure of active site inhibited coagulation factor VIIA mutant in complex with soluble tissue factor===
+Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity.,Bjelke JR, Olsen OH, Fodje M, Svensson LA, Bang S, Bolt G, Kragelund BB, Persson E J Biol Chem. 2008 Sep 19;283(38):25863-70. Epub 2008 Jul 17. PMID:18640965<ref>PMID:18640965</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3ela" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18640965}}, adds the Publication Abstract to the page
+*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18640965 is the PubMed ID number.
+*[[Tissue factor|Tissue factor]]
--->
+== References ==
-{{ABSTRACT_PUBMED_18640965}}
+<references/>
+__TOC__
-==Disease==
+</StructureSection>
-Known disease associated with this structure: Factor VII deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]], Myocardial infarction, decreased susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227500 227500]]
-==About this Structure==
-ELA is a [[Protein complex]] structure of sequences 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=3ELA OCA].
-==Reference==
-Mechanism of the Ca2+-induced enhancement of the intrinsic factor VIIa activity., Bjelke JR, Olsen OH, Fodje M, Svensson LA, Bang S, Bolt G, Kragelund BB, Persson E, J Biol Chem. 2008 Sep 19;283(38):25863-70. Epub 2008 Jul 17. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18640965 18640965]
-[[Category: Coagulation factor VIIa]]
 [[Category: Homo sapiens]]
-[[Category: Protein complex]]
+[[Category: Large Structures]]
-[[Category: Bjelke, J R.]]
+[[Category: Bjelke JR]]
-[[Category: Fodje, M.]]
+[[Category: Fodje M]]
-[[Category: Svensson, L A.]]
+[[Category: Svensson LA]]
-[[Category: Allosteric regulation]]
-[[Category: Allostery]]
-[[Category: Alternative splicing]]
-[[Category: Blood clotting]]
-[[Category: Blood coagulation]]
-[[Category: Calcium]]
-[[Category: Cleavage on pair of basic residue]]
-[[Category: Disease mutation]]
-[[Category: Egf-like domain]]
-[[Category: Exosite]]
-[[Category: Gamma-carboxyglutamic acid]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Hydroxylation]]
-[[Category: Lipoprotein]]
-[[Category: Membrane]]
-[[Category: Palmitate]]
-[[Category: Pharmaceutical]]
-[[Category: Polymorphism]]
-[[Category: Protease]]
-[[Category: Secreted]]
-[[Category: Serine protease]]
-[[Category: Transmembrane]]
-[[Category: Zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Nov  5 12:56:26 2008''