4h6s - Revision history

OCA at 15:01, 20 September 2023

OCA — Wed, 20 Sep 2023 15:01:07 GMT

←Older revision		Revision as of 15:01, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4h6s]] is a 2 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=4H6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H6S FirstGlance]. <br>		<table><tr><td colspan='2'>[[4h6s]] is a 2 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=4H6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H6S FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 2.19Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [https://pdbe.org/4h6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [https://www.ebi.ac.uk/pdbsum/4h6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6s 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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [https://pdbe.org/4h6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [https://www.ebi.ac.uk/pdbsum/4h6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6s ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:02, 3 November 2022

OCA — Thu, 03 Nov 2022 08:02:37 GMT

←Older revision		Revision as of 08:02, 3 November 2022
Line 1:		Line 1:

	==Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A==		==Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A==
-	<StructureSection load='4h6s' size='340' side='right' caption='[[4h6s]], [[Resolution\|resolution]] 2.19Å' scene=''>	+	<StructureSection load='4h6s' size='340' side='right'caption='[[4h6s]], [[Resolution\|resolution]] 2.19Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4h6s]] is a 2 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=4H6S OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4H6S FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4h6s]] is a 2 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=4H6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4H6S FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4h6t\|4h6t]]</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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [https://pdbe.org/4h6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [https://www.ebi.ac.uk/pdbsum/4h6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6s ProSAT]</span></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [~~http~~://pdbe.org/4h6s PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4h6s PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6s ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[~~http~~://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[~~http~~://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[~~http~~://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[~~http~~://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>	+	[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>	+	[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
-	*[[Thrombin\|Thrombin]]	+	*[[Thrombin 3D Structures\|Thrombin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Thrombin~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Cera, E Di~~]]	+	[[Category: Chen Z]]
-	[[Category: ~~Chen, Z~~]]	+	[[Category: Di Cera E]]
-	[[Category: Pelc~~, L A~~]]	+	[[Category: Pelc LA]]
-	[[Category: Pozzi, N]]	+	[[Category: Pozzi N]]
-	[[Category: Zapata, F]]	+	[[Category: Zapata F]]
-	~~[[Category: Autoactivation]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase-peptide complex]]~~	+
-	~~[[Category: Prethrombin-2]]~~	+
-	~~[[Category: Serine protease~~]]	+

OCA at 10:40, 11 August 2016

OCA — Thu, 11 Aug 2016 10:40:36 GMT

←Older revision		Revision as of 10:40, 11 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A==		==Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A==
	<StructureSection load='4h6s' size='340' side='right' caption='[[4h6s]], [[Resolution\|resolution]] 2.19Å' scene=''>		<StructureSection load='4h6s' size='340' side='right' caption='[[4h6s]], [[Resolution\|resolution]] 2.19Å' scene=''>
Line 7:		Line 8:
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F2 ([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">F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [http://www.ebi.ac.uk/pdbsum/4h6s 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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [http://pdbe.org/4h6s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [http://www.ebi.ac.uk/pdbsum/4h6s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4h6s ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 4h6s" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 14:34, 4 January 2015

OCA — Sun, 04 Jan 2015 14:34:25 GMT

←Older revision		Revision as of 14:34, 4 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4h6s]] is a 2 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=4H6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H6S FirstGlance]. <br>		<table><tr><td colspan='2'>[[4h6s]] is a 2 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=4H6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H6S FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4h6t\|4h6t]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4h6t\|4h6t]]</td></tr>
-	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F2 ([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">F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [http://www.ebi.ac.uk/pdbsum/4h6s 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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [http://www.ebi.ac.uk/pdbsum/4h6s PDBsum]</span></td></tr>
-	<table>	+	</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[http://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[http://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[http://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>		[[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[http://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[http://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[http://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
Line 30:		Line 30:
	[[Category: Human]]		[[Category: Human]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
-	[[Category: Cera, E Di.]]	+	[[Category: Cera, E Di]]
-	[[Category: Chen, Z.]]	+	[[Category: Chen, Z]]
-	[[Category: Pelc, L A.]]	+	[[Category: Pelc, L A]]
-	[[Category: Pozzi, N.]]	+	[[Category: Pozzi, N]]
-	[[Category: Zapata, F.]]	+	[[Category: Zapata, F]]
	[[Category: Autoactivation]]		[[Category: Autoactivation]]
	[[Category: Hydrolase]]		[[Category: Hydrolase]]

OCA at 07:20, 11 June 2014

OCA — Wed, 11 Jun 2014 07:20:01 GMT

←Older revision		Revision as of 07:20, 11 June 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4h6s\| PDB=4h6s \| SCENE= }}~~	+	==Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A==
-	===Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A===	+	<StructureSection load='4h6s' size='340' side='right' caption='[[4h6s]], [[Resolution\|resolution]] 2.19Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4h6s]] is a 2 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=4H6S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H6S FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4h6t\|4h6t]]</td></tr>
		+	<tr><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">F2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></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=4h6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h6s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h6s RCSB], [http://www.ebi.ac.uk/pdbsum/4h6s PDBsum]</span></td></tr>
		+	<table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[http://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[http://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[http://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Trypsin-like proteases are synthesized as inactive zymogens and convert to the mature form upon activation by specific enzymes, often assisted by cofactors. Central to this paradigm is that the zymogen does not convert spontaneously to the mature enzyme, which in turn does not feed back to activate its zymogen form. In the blood, the zymogens prothrombin and prethrombin-2 require the prothrombinase complex to be converted to the mature protease thrombin, which is unable to activate prothrombin or prethrombin-2. Here, we show that replacement of key residues within the activation domain causes these zymogens to spontaneously convert to thrombin. The conversion is started by the zymogen itself, which is capable of binding ligands at the active site, and is abrogated by inactivation of the catalytic residue Ser-195. The product of autoactivation is functionally and structurally equivalent to wild-type thrombin. Zymogen autoactivation is explained by conformational selection, a basic property of the trypsin fold uncovered by structural and rapid kinetics studies. Both the zymogen and protease undergo a pre-existing equilibrium between active and inactive forms. The equilibrium regulates catalytic activity in the protease and has the potential to unleash activity in the zymogen to produce autoactivation. A new strategy emerges for the facile production of enzymes through zymogen autoactivation that is broadly applicable to trypsin-like proteases of biotechnological and clinical interest.

-	~~==About this Structure==~~	+	Autoactivation of thrombin precursors.,Pozzi N, Chen Z, Zapata F, Niu W, Barranco-Medina S, Pelc LA, Di Cera E J Biol Chem. 2013 Apr 19;288(16):11601-10. doi: 10.1074/jbc.M113.451542. Epub, 2013 Mar 6. PMID:23467412<ref>PMID:23467412</ref>
-	~~[[4h6s]] is a 2 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~~=~~4H6S OCA~~].	+
-	[[Category: ~~Homo sapiens~~]]	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+
		+	==See Also==
		+	*[[Thrombin\|Thrombin]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Cera, E Di.]]		[[Category: Cera, E Di.]]

OCA at 10:30, 13 March 2013

OCA — Wed, 13 Mar 2013 10:30:12 GMT

←Older revision		Revision as of 10:30, 13 March 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4h6s\| PDB=4h6s \| SCENE= }}
		+	===Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A===

-	~~The entry~~ 4h6s is ~~ON HOLD until Paper Publication~~	+	==About this Structure==
-		+	[[4h6s]] is a 2 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=4H6S OCA].
-	~~Authors~~: ~~Pozzi~~, N., Chen, Z.~~, Zapata, F.,~~ Pelc, L.A., ~~Di Cera~~, E.	+	[[Category: Homo sapiens]]
-		+	[[Category: Thrombin]]
-	~~Description~~: ~~Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A~~	+	[[Category: Cera, E Di.]]
		+	[[Category: Chen, Z.]]
		+	[[Category: Pelc, L A.]]
		+	[[Category: Pozzi, N.]]
		+	[[Category: Zapata, F.]]
		+	[[Category: Autoactivation]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase-peptide complex]]
		+	[[Category: Prethrombin-2]]
		+	[[Category: Serine protease]]

OCA at 13:20, 8 November 2012

OCA — Thu, 08 Nov 2012 13:20:21 GMT

←Older revision		Revision as of 13:20, 8 November 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4h6s is ON HOLD	+	The entry 4h6s is ON HOLD until Paper Publication

	Authors: Pozzi, N., Chen, Z., Zapata, F., Pelc, L.A., Di Cera, E.		Authors: Pozzi, N., Chen, Z., Zapata, F., Pelc, L.A., Di Cera, E.

	Description: Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A		Description: Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A

OCA at 05:48, 3 October 2012

OCA — Wed, 03 Oct 2012 05:48:23 GMT

←Older revision		Revision as of 05:48, 3 October 2012
Line 3:		Line 3:
	The entry 4h6s is ON HOLD		The entry 4h6s is ON HOLD

-	Authors: Pozzi, N., Chen, Z., Zapata, F., Pelc, L. A., Di Cera, E.	+	Authors: Pozzi, N., Chen, Z., Zapata, F., Pelc, L.A., Di Cera, E.

	Description: Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A		Description: Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A

OCA: Protected "4h6s" [edit=sysop:move=sysop]

OCA — Wed, 26 Sep 2012 20:14:29 GMT

Protected "4h6s" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:14, 26 September 2012

OCA: New page: '''Unreleased structure''' The entry 4h6s is ON HOLD Authors: Pozzi, N., Chen, Z., Zapata, F., Pelc, L. A., Di Cera, E. Description: Crystal structure of thrombin mutant E14eA/D14lA/E1...

OCA — Wed, 26 Sep 2012 20:14:28 GMT

New page: '''Unreleased structure''' The entry 4h6s is ON HOLD Authors: Pozzi, N., Chen, Z., Zapata, F., Pelc, L. A., Di Cera, E. Description: Crystal structure of thrombin mutant E14eA/D14lA/E1...

New page

'''Unreleased structure'''

The entry 4h6s is ON HOLD

Authors: Pozzi, N., Chen, Z., Zapata, F., Pelc, L. A., Di Cera, E.

Description: Crystal structure of thrombin mutant E14eA/D14lA/E18A/S195A