1w0y: Difference between revisions

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[[Image:1w0y.gif|left|200px]]<br />
<applet load="1w0y" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1w0y, resolution 2.50&Aring;" />
'''TF7A_3771 COMPLEX'''<br />


==Overview==
==tf7a_3771 complex==
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.
<StructureSection load='1w0y' size='340' side='right'caption='[[1w0y]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<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='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='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='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>
</table>
== Function ==
[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 ==
[[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/w0/1w0y_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=1w0y ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== 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.


==Disease==
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<ref>PMID:15664864</ref>
Known diseases associated with this structure: Esophageal squamous cell carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606551 606551]], 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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1W0Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with FUC, BGC, CA, CAC and 771 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1W0Y OCA].
</div>
<div class="pdbe-citations 1w0y" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15664864 15664864]
*[[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: 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: 771]]
[[Category: BGC]]
[[Category: CA]]
[[Category: CAC]]
[[Category: FUC]]
[[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]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:45:54 2007''

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

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