Proteopedia

2f9b: Difference between revisions

← Older edit
No edit summary
No edit summary
 
(16 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:2f9b.gif|left|200px]]<br /><applet load="2f9b" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2f9b, resolution 2.54&Aring;" />
'''Discovery of Novel Heterocyclic Factor VIIa Inhibitors'''<br />


==Overview==
==Discovery of Novel Heterocyclic Factor VIIa Inhibitors==
<StructureSection load='2f9b' size='340' side='right'caption='[[2f9b]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2f9b]] 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=2F9B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F9B 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]] 2.54&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=N1H:{5-(5-AMINO-1H-PYRROLO[3,2-B]PYRIDIN-2-YL)-6-HYDROXY-3-NITRO-BIPHENYL-3-YL]-ACETIC+ACID'>N1H</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=2f9b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f9b OCA], [https://pdbe.org/2f9b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f9b RCSB], [https://www.ebi.ac.uk/pdbsum/2f9b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f9b 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/f9/2f9b_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=2f9b ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Structure-activity relationships and binding mode of novel heterocyclic factor VIIa inhibitors will be described. In these inhibitors, a highly basic 5-amidinoindole moiety has been successfully replaced with a less basic 5-aminopyrrolo[3,2-b]pyridine scaffold.
Structure-activity relationships and binding mode of novel heterocyclic factor VIIa inhibitors will be described. In these inhibitors, a highly basic 5-amidinoindole moiety has been successfully replaced with a less basic 5-aminopyrrolo[3,2-b]pyridine scaffold.


==Disease==
Discovery of novel heterocyclic factor VIIa inhibitors.,Rai R, Kolesnikov A, Sprengeler PA, Torkelson S, Ton T, Katz BA, Yu C, Hendrix J, Shrader WD, Stephens R, Cabuslay R, Sanford E, Young WB Bioorg Med Chem Lett. 2006 Apr 15;16(8):2270-3. Epub 2006 Feb 3. PMID:16460932<ref>PMID:16460932</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>
2F9B 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 <scene name='pdbligand=N1H:'>N1H</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F9B OCA].
</div>
<div class="pdbe-citations 2f9b" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Discovery of novel heterocyclic factor VIIa inhibitors., Rai R, Kolesnikov A, Sprengeler PA, Torkelson S, Ton T, Katz BA, Yu C, Hendrix J, Shrader WD, Stephens R, Cabuslay R, Sanford E, Young WB, Bioorg Med Chem Lett. 2006 Apr 15;16(8):2270-3. Epub 2006 Feb 3. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16460932 16460932]
*[[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: Cabuslay, R.]]
[[Category: Cabuslay R]]
[[Category: Hendrix, J.]]
[[Category: Hendrix J]]
[[Category: Katz, B A.]]
[[Category: Katz BA]]
[[Category: Kolesnikov, A.]]
[[Category: Kolesnikov A]]
[[Category: Rai, R.]]
[[Category: Rai R]]
[[Category: Sanford, E.]]
[[Category: Sanford E]]
[[Category: Shrader, W D.]]
[[Category: Shrader WD]]
[[Category: Sprengeler, P A.]]
[[Category: Sprengeler PA]]
[[Category: Stephens, R.]]
[[Category: Stephens R]]
[[Category: Ton, T.]]
[[Category: Ton T]]
[[Category: Torkelson, S.]]
[[Category: Torkelson S]]
[[Category: Young, W B.]]
[[Category: Young WB]]
[[Category: Yu, C.]]
[[Category: Yu C]]
[[Category: N1H]]
[[Category: active site-directed inhibitor]]
[[Category: serine protease]]
[[Category: short hydrogen bond]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:19:02 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/2f9b"