Proteopedia

1wtg: Difference between revisions

← Older edit
No edit summary
No edit summary
 
(12 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1wtg.gif|left|200px]]
<!--
The line below this paragraph, containing "STRUCTURE_1wtg", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet)
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_1wtg|  PDB=1wtg  |  SCENE=  }}
'''Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine'''


==Human Factor Viia-Tissue Factor Complexed with ethylsulfonamide-D-biphenylalanine-Gln-p-aminobenzamidine==
<StructureSection load='1wtg' size='340' side='right'caption='[[1wtg]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1wtg]] 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=1WTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WTG 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3BP:2-(3-BIPHENYL-4-YL-2-ETHANESULFONYLAMINO-PROPIONYLAMINO)-PENTANEDIOIC+ACID+5-AMIDE+1-(4-CARBAMIMIDOYL-BENZYLAMIDE)'>3BP</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</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=1wtg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wtg OCA], [https://pdbe.org/1wtg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wtg RCSB], [https://www.ebi.ac.uk/pdbsum/1wtg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wtg 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/wt/1wtg_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=1wtg ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF.


==Overview==
Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor.,Kadono S, Sakamoto A, Kikuchi Y, Oh-Eda M, Yabuta N, Yoshihashi K, Kitazawa T, Suzuki T, Koga T, Hattori K, Shiraishi T, Haramura M, Kodama H, Ono Y, Esaki T, Sato H, Watanabe Y, Itoh S, Ohta M, Kozono T Biochem Biophys Res Commun. 2005 Jan 28;326(4):859-65. PMID:15607748<ref>PMID:15607748</ref>
Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is seen as a promising target for developing new anticoagulant drugs. A novel peptide mimetic factor VIIa inhibitor, ethylsulfonamide-d-biphenylalanine-Gln-p-aminobenzamidine, shows 100-fold selectivity against thrombin in spite of its large P3 moiety, unlike previously reported FVIIa/TF selective inhibitors. X-ray crystal structure analysis reveals that the large P3 moiety, d-biphenylalanine, and the small P4 moiety, ethylsulfonamide, make novel interactions with the 170-loop and Lys192 of FVIIa/TF, respectively, accompanying ligand-induced conformational changes of the 170-loop, Gln217, and Lys192. Structural comparisons of FVIIa with thrombin and amino acid sequence comparisons among coagulation serine proteases suggest that these interactions play an important role in achieving selective inhibition for FVIIa/TF.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1WTG 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=1WTG OCA].
</div>
<div class="pdbe-citations 1wtg" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Novel interactions of large P3 moiety and small P4 moiety in the binding of the peptide mimetic factor VIIa inhibitor., Kadono S, Sakamoto A, Kikuchi Y, Oh-Eda M, Yabuta N, Yoshihashi K, Kitazawa T, Suzuki T, Koga T, Hattori K, Shiraishi T, Haramura M, Kodama H, Ono Y, Esaki T, Sato H, Watanabe Y, Itoh S, Ohta M, Kozono T, Biochem Biophys Res Commun. 2005 Jan 28;326(4):859-65. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15607748 15607748]
*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
[[Category: Coagulation factor VIIa]]
*[[Tissue factor|Tissue factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Large Structures]]
[[Category: Esaki, T.]]
[[Category: Esaki T]]
[[Category: Haramura, H.]]
[[Category: Haramura H]]
[[Category: Hattori, K.]]
[[Category: Hattori K]]
[[Category: Itoh, S.]]
[[Category: Itoh S]]
[[Category: Kadono, S.]]
[[Category: Kadono S]]
[[Category: Kikuchi, Y.]]
[[Category: Kikuchi Y]]
[[Category: Kitazawa, K.]]
[[Category: Kitazawa K]]
[[Category: Kodama, M.]]
[[Category: Kodama M]]
[[Category: Koga, T.]]
[[Category: Koga T]]
[[Category: Kozono, T.]]
[[Category: Kozono T]]
[[Category: Oh-Eda, M.]]
[[Category: Oh-Eda M]]
[[Category: Ohta, M.]]
[[Category: Ohta M]]
[[Category: Ono, Y.]]
[[Category: Ono Y]]
[[Category: Sakamoto, S.]]
[[Category: Sakamoto S]]
[[Category: Sato, H.]]
[[Category: Sato H]]
[[Category: Shiraishi, T.]]
[[Category: Shiraishi T]]
[[Category: Suzuki, T.]]
[[Category: Suzuki T]]
[[Category: Watanabe, Y.]]
[[Category: Watanabe Y]]
[[Category: Yabuta, N.]]
[[Category: Yabuta N]]
[[Category: Yoshihashi, T.]]
[[Category: Yoshihashi T]]
[[Category: Serine protease]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 14:06:55 2008''

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/w/1wtg"