2flb - Revision history

OCA at 15:28, 3 March 2021

2021-03-03T15:28:45Z

← Older revision		Revision as of 15:28, 3 March 2021
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	==Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor==		==Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor==
	<StructureSection load='2flb' size='340' side='right' caption='[[2flb]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2flb' size='340' side='right'caption='[[2flb]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2flb]] 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=2FLB OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=2FLB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2flb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FLB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FLB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NH:2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>6NH</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NH:2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>6NH</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1o5d\|1o5d]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), F3 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), F3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [~~http~~://pdbe.org/2flb PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/2flb PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=2flb ProSAT]</span></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=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [https://pdbe.org/2flb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [https://www.ebi.ac.uk/pdbsum/2flb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2flb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>		[[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 ==		== 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/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. [[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/fl/2flb_consurf.spt"</scriptWhenChecked>		<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fl/2flb_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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	</div>		</div>
	<div class="pdbe-citations 2flb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2flb" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Tissue factor\|Tissue factor]]
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
			[[Category: Large Structures]]
	[[Category: Katz, B A]]		[[Category: Katz, B A]]
	[[Category: Active site-directed]]		[[Category: Active site-directed]]

OCA at 15:14, 12 October 2017

2017-10-12T15:14:22Z

← Older revision		Revision as of 15:14, 12 October 2017
Line 1:		Line 1:

	==Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor==		==Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor==
	<StructureSection load='2flb' size='340' side='right' caption='[[2flb]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2flb' size='340' side='right' caption='[[2flb]], [[Resolution\|resolution]] 1.95Å' scene=''>
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	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [http://pdbe.org/2flb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [http://www.ebi.ac.uk/pdbsum/2flb PDBsum]</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=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [http://pdbe.org/2flb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [http://www.ebi.ac.uk/pdbsum/2flb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2flb ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	</div>		</div>
	<div class="pdbe-citations 2flb" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 2flb" style="background-color:#fffaf0;"></div>

	~~==See Also==~~
	*[[Tissue factor\|Tissue factor]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:27, 7 February 2016

2016-02-07T16:27:01Z

← Older revision		Revision as of 16:27, 7 February 2016
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	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</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/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].		</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=2flb ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 03:13, 10 September 2015

2015-09-10T03:13:58Z

← Older revision		Revision as of 03:13, 10 September 2015
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	<StructureSection load='2flb' size='340' side='right' caption='[[2flb]], [[Resolution\|resolution]] 1.95Å' scene=''>		<StructureSection load='2flb' size='340' side='right' caption='[[2flb]], [[Resolution\|resolution]] 1.95Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2flb]] is a 3 chain structure with sequence 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=2FLB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FLB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2flb]] 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=2FLB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FLB FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NH:2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>6NH</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NH:2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>6NH</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [http://www.ebi.ac.uk/pdbsum/2flb PDBsum]</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=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [http://pdbe.org/2flb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [http://www.ebi.ac.uk/pdbsum/2flb PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
			<div class="pdbe-citations 2flb" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Homo sapiens~~]]		[[Category: Human]]
	[[Category: Katz, B A]]		[[Category: Katz, B A]]
	[[Category: Active site-directed]]		[[Category: Active site-directed]]

OCA at 08:57, 16 January 2015

2015-01-16T08:57:07Z

← Older revision		Revision as of 08:57, 16 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[2flb]] is a 3 chain structure with sequence 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=2FLB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FLB FirstGlance]. <br>		<table><tr><td colspan='2'>[[2flb]] is a 3 chain structure with sequence 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=2FLB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FLB FirstGlance]. <br>
	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NH:2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>6NH</scene><br>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NH:2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>6NH</scene></td></tr>
	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>
	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
	<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [http://www.ebi.ac.uk/pdbsum/2flb PDBsum]</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=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [http://www.ebi.ac.uk/pdbsum/2flb PDBsum]</span></td></tr>
	<table>		</table>
	== Disease ==		== 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>		[[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>
Line 38:		Line 38:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Katz, B A.]]		[[Category: Katz, B A]]
	[[Category: Active site-directed]]		[[Category: Active site-directed]]
	[[Category: Hydrolase-blood clotting complex]]		[[Category: Hydrolase-blood clotting complex]]
	[[Category: Pyrazole-based inhibitor]]		[[Category: Pyrazole-based inhibitor]]
	[[Category: Short hydrogen bond-mediated]]		[[Category: Short hydrogen bond-mediated]]

OCA at 02:30, 30 September 2014

2014-09-30T02:30:19Z

← Older revision		Revision as of 02:30, 30 September 2014
Line 1:		Line 1:
	~~{{STRUCTURE_2flb~~\| ~~PDB~~=2flb \| ~~SCENE~~= }}		==Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor==
	===~~Discovery~~ of a ~~Novel Hydroxy Pyrazole Based~~ Factor IXa ~~Inhibitor~~===		<StructureSection load='2flb' size='340' side='right' caption='[[2flb]], [[Resolution\|resolution]] 1.95Å' scene=''>
	~~{{ABSTRACT_PUBMED_16487703}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[2flb]] is a 3 chain structure with sequence 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=2FLB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FLB FirstGlance]. <br>
			</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6NH:2-(4-HYDROXY-5-PHENYL-1H-PYRAZOL-3-YL)-1H-BENZOIMIDAZOLE-5-CARBOXAMIDINE'>6NH</scene><br>
			<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1o5d\|1o5d]]</td></tr>
			<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), F3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
			<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2flb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2flb OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2flb RCSB], [http://www.ebi.ac.uk/pdbsum/2flb PDBsum]</span></td></tr>
			<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 ==
			[[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>
			== 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/fl/2flb_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/chain_selection.php?pdb_ID=2ata ConSurf].
			<div style="clear:both"></div>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Synthesis and biological data of a novel selective and efficacious factor IXa inhibitor are described along with its crystal structure in factor VIIa.

	~~==Disease==~~		Discovery of novel hydroxy pyrazole based factor IXa inhibitor.,Vijaykumar D, Sprengeler PA, Shaghafi M, Spencer JR, Katz BA, Yu C, Rai R, Young WB, Schultz B, Janc J Bioorg Med Chem Lett. 2006 May 15;16(10):2796-9. Epub 2006 Feb 17. PMID:16487703<ref>PMID:16487703</ref>
	~~[[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==~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[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~~>		</div>

	==~~About this Structure~~==		==See Also==
	[[~~2flb~~]] is a 3 chain structure with sequence 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=2FLB OCA].		*[[Tissue factor\|Tissue factor]]
			== References ==
	==~~Reference~~==		<references/>
	~~<ref group="xtra">PMID:016487703</ref>~~<references ~~group="xtra"~~/><~~references~~/>		__TOC__
			</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Katz, B A.]]		[[Category: Katz, B A.]]

OCA at 21:48, 24 March 2013

2013-03-24T21:48:13Z

← Older revision		Revision as of 21:48, 24 March 2013
Line 1:		Line 1:
	~~[[Image:2flb.png\|left\|200px]]~~

	{{STRUCTURE_2flb\| PDB=2flb \| SCENE= }}		{{STRUCTURE_2flb\| PDB=2flb \| SCENE= }}
			===Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor===
			{{ABSTRACT_PUBMED_16487703}}

	===~~Discovery~~ of a ~~Novel Hydroxy Pyrazole Based Factor IXa Inhibitor===~~		==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>

	~~{{ABSTRACT_PUBMED_16487703}}~~		==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>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
	<ref group="xtra">PMID:016487703</ref><references group="xtra"/>		<ref group="xtra">PMID:016487703</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Katz, B A.]]		[[Category: Katz, B A.]]

OCA: Protected "2flb" [edit=sysop:move=sysop]

2013-01-07T14:55:38Z

Protected "2flb" [edit=sysop:move=sysop]

← Older revision	Revision as of 14:55, 7 January 2013
(No difference)

OCA at 14:55, 7 January 2013

2013-01-07T14:55:34Z

← Older revision		Revision as of 14:55, 7 January 2013
Line 1:		Line 1:
	~~{{Seed}}~~
	[[Image:2flb.png\|left\|200px]]		[[Image:2flb.png\|left\|200px]]

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_2flb", 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_2flb\| PDB=2flb \| SCENE= }}		{{STRUCTURE_2flb\| PDB=2flb \| SCENE= }}

	===Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor===		===Discovery of a Novel Hydroxy Pyrazole Based Factor IXa Inhibitor===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_16487703}}, adds the Publication Abstract to the page~~
	~~(as it appears on PubMed at http://www.pubmed.gov), where 16487703 is the PubMed ID number.~~
	~~-->~~
	{{ABSTRACT_PUBMED_16487703}}		{{ABSTRACT_PUBMED_16487703}}

	~~==Disease==~~
	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==		==About this Structure==
	~~2FLB~~ is a 3 ~~chains~~ 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=2FLB OCA].		[[2flb]] is a 3 chain structure with sequence 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=2FLB OCA].

	==Reference==		==Reference==
	<ref group="xtra">PMID:~~16487703~~</ref><references group="xtra"/>		<ref group="xtra">PMID:016487703</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Katz, B A.]]		[[Category: Katz, B A.]]
	[[Category: Active site-directed]]		[[Category: Active site-directed]]
			[[Category: Hydrolase-blood clotting complex]]
	[[Category: Pyrazole-based inhibitor]]		[[Category: Pyrazole-based inhibitor]]
	[[Category: Short hydrogen bond-mediated]]		[[Category: Short hydrogen bond-mediated]]

	~~''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 15:06:23 2009''~~

OCA at 13:06, 16 February 2009

2009-02-16T13:06:24Z

← Older revision		Revision as of 13:06, 16 February 2009
Line 23:		Line 23:

	==About this Structure==		==About this Structure==
	2FLB 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=2FLB OCA].		2FLB is a 3 chains 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=2FLB OCA].

	==Reference==		==Reference==
	Discovery of novel hydroxy pyrazole based factor IXa inhibitor., Vijaykumar D, Sprengeler PA, Shaghafi M, Spencer JR, Katz BA, Yu C, Rai R, Young WB, Schultz B, Janc J, Bioorg Med Chem Lett. 2006 May 15;16(10):2796-9. Epub 2006 Feb 17. PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/16487703 16487703]~~		<ref group="xtra">PMID:16487703</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	~~[[Category: Protein complex]]~~
	[[Category: Katz, B A.]]		[[Category: Katz, B A.]]
	[[Category: Active site-directed]]		[[Category: Active site-directed]]
Line 34:		Line 33:
	[[Category: Short hydrogen bond-mediated]]		[[Category: Short hydrogen bond-mediated]]

	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sun Jul 27 17~~:55:~~22 2008~~''		''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 15:06:23 2009''