1w0y: Difference between revisions

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==TF7A_3771 COMPLEX==
 
<StructureSection load='1w0y' size='340' side='right' caption='[[1w0y]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
==tf7a_3771 complex==
<StructureSection load='1w0y' size='340' side='right'caption='[[1w0y]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1w0y]] 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=1W0Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W0Y FirstGlance]. <br>
<table><tr><td colspan='2'>[[1w0y]] 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=1W0Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W0Y FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=771:4-(4-BENZYLOXY-2-METHANESULFONYLAMINO-5-METHOXY-BENZYLAMINO)-BENZAMIDINE'>771</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='NonStdRes'><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>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=771:4-(4-BENZYLOXY-2-METHANESULFONYLAMINO-5-METHOXY-BENZYLAMINO)-BENZAMIDINE'>771</scene>, <scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=CGU:GAMMA-CARBOXY-GLUTAMIC+ACID'>CGU</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bf9|1bf9]], [[1cvw|1cvw]], [[1dan|1dan]], [[1dva|1dva]], [[1f7e|1f7e]], [[1f7m|1f7m]], [[1ff7|1ff7]], [[1ffm|1ffm]], [[1jbu|1jbu]], [[1kli|1kli]], [[1klj|1klj]], [[1qfk|1qfk]], [[1ahw|1ahw]], [[1boy|1boy]], [[1fak|1fak]], [[1jps|1jps]], [[1tfh|1tfh]], [[1w2k|1w2k]], [[2hft|2hft]]</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=1w0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0y OCA], [https://pdbe.org/1w0y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w0y RCSB], [https://www.ebi.ac.uk/pdbsum/1w0y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w0y ProSAT]</span></td></tr>
<tr id='activity'><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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w0y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w0y OCA], [http://pdbe.org/1w0y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w0y RCSB], [http://www.ebi.ac.uk/pdbsum/1w0y PDBsum]</span></td></tr>
</table>
</table>
== Disease ==
[[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> 
== Function ==
== Function ==
[[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>
[https://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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w0/1w0y_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w0/1w0y_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
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==See Also==
==See Also==
*[[Factor VIIa|Factor VIIa]]
*[[Factor VIIa 3D structures|Factor VIIa 3D structures]]
*[[Tissue factor|Tissue factor]]
*[[Tissue factor|Tissue factor]]
== References ==
== References ==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Coagulation factor VIIa]]
[[Category: Homo sapiens]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Ackermann, J]]
[[Category: Ackermann J]]
[[Category: Arcy, A D]]
[[Category: Banner DW]]
[[Category: Banner, D W]]
[[Category: D'Arcy A]]
[[Category: Groebke-Zbinden, K]]
[[Category: Groebke-Zbinden K]]
[[Category: Ji, Y H]]
[[Category: Ji Y-H]]
[[Category: Kirchhofer, D]]
[[Category: Kirchhofer D]]
[[Category: Tschopp, T B]]
[[Category: Tschopp TB]]
[[Category: Wallbaum, S]]
[[Category: Wallbaum S]]
[[Category: Weber, L]]
[[Category: Weber L]]
[[Category: Blood coagulation]]
[[Category: Calcium-binding]]
[[Category: Co-factor]]
[[Category: Coagulation]]
[[Category: Enzyme complex]]
[[Category: Gamma-carboxyglutamic acid]]
[[Category: Glycoprotein]]
[[Category: Hydrolase]]
[[Category: Plasma]]
[[Category: Serine protease]]
[[Category: Vitamin k]]

Latest revision as of 16:11, 13 December 2023

tf7a_3771 complextf7a_3771 complex

Structural highlights

1w0y is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.5Å
Ligands:, , , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Proof of concept experiments have shown that tissue factor/factor VIIa inhibitors have antithrombotic activity without enhancing bleeding propensity. Starting from lead compounds generated by a biased combinatorial approach, phenylglycine amide tissue factor/factor VIIa inhibitors with low nanomolar affinity and good selectivity against other serine proteases of the coagulation cascade were designed, using the guidance of X-ray structural analysis and molecular modelling.

Design of selective phenylglycine amide tissue factor/factor VIIa inhibitors.,Groebke Zbinden K, Banner DW, Ackermann J, D'Arcy A, Kirchhofer D, Ji YH, Tschopp TB, Wallbaum S, Weber L Bioorg Med Chem Lett. 2005 Feb 1;15(3):817-22. PMID:15664864[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Bogdanov VY, Balasubramanian V, Hathcock J, Vele O, Lieb M, Nemerson Y. Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med. 2003 Apr;9(4):458-62. Epub 2003 Mar 24. PMID:12652293 doi:10.1038/nm841
  2. Groebke Zbinden K, Banner DW, Ackermann J, D'Arcy A, Kirchhofer D, Ji YH, Tschopp TB, Wallbaum S, Weber L. Design of selective phenylglycine amide tissue factor/factor VIIa inhibitors. Bioorg Med Chem Lett. 2005 Feb 1;15(3):817-22. PMID:15664864 doi:10.1016/j.bmcl.2004.10.092

1w0y, resolution 2.50Å

Drag the structure with the mouse to rotate

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OCA