4rko - Revision history

OCA at 17:51, 20 September 2023

OCA — Wed, 20 Sep 2023 17:51:22 GMT

←Older revision		Revision as of 17:51, 20 September 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4rko]] 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=4RKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RKO FirstGlance]. <br>		<table><tr><td colspan='2'>[[4rko]] 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=4RKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RKO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 1.84Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [https://pdbe.org/4rko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [https://www.ebi.ac.uk/pdbsum/4rko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rko 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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [https://pdbe.org/4rko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [https://www.ebi.ac.uk/pdbsum/4rko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rko ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:01, 2 March 2023

OCA — Thu, 02 Mar 2023 07:01:22 GMT

←Older revision		Revision as of 07:01, 2 March 2023
Line 3:		Line 3:
	<StructureSection load='4rko' size='340' side='right'caption='[[4rko]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='4rko' size='340' side='right'caption='[[4rko]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rko]] 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=4RKO OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4RKO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rko]] 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=4RKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RKO FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene~~></td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4rkj\|4rkj]]</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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [https://pdbe.org/4rko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [https://www.ebi.ac.uk/pdbsum/4rko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rko 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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [~~http~~://pdbe.org/4rko PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4rko PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4rko 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: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Thrombin~~]]	+	[[Category: Chen Z]]
-	[[Category: Cera, E ~~Di]]~~	+	[[Category: Di Cera E]]
-	~~[[Category: Chen, Z~~]]	+	[[Category: Gohara DW]]
-	[[Category: Gohara~~, D W~~]]	+	[[Category: Pelc AL]]
-	[[Category: Pelc~~, A L~~]]	+	[[Category: Pozzi N]]
-	[[Category: Pozzi, N]]	+	[[Category: Vogt AD]]
-	[[Category: Vogt~~, A D]]~~	+
-	~~[[Category: Allosteric regulation]]~~	+
-	~~[[Category: Catalysis]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Trypsin-like protease~~]]	+

OCA at 09:46, 1 May 2019

OCA — Wed, 01 May 2019 09:46:45 GMT

←Older revision		Revision as of 09:46, 1 May 2019
Line 1:		Line 1:

	==Crystal structure of thrombin mutant S195T bound with PPACK==		==Crystal structure of thrombin mutant S195T bound with PPACK==
-	<StructureSection load='4rko' size='340' side='right' caption='[[4rko]], [[Resolution\|resolution]] 1.84Å' scene=''>	+	<StructureSection load='4rko' size='340' side='right'caption='[[4rko]], [[Resolution\|resolution]] 1.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4rko]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RKO FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4rko]] 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=4RKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RKO FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4rkj\|4rkj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4rkj\|4rkj]]</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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [http://pdbe.org/4rko PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [http://www.ebi.ac.uk/pdbsum/4rko PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rko ProSAT]</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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [http://pdbe.org/4rko PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [http://www.ebi.ac.uk/pdbsum/4rko PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rko ProSAT]</span></td></tr>
Line 29:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Cera, E Di]]		[[Category: Cera, E Di]]

OCA at 17:23, 18 January 2017

OCA — Wed, 18 Jan 2017 17:23:17 GMT

←Older revision		Revision as of 17:23, 18 January 2017
Line 1:		Line 1:
		+
	==Crystal structure of thrombin mutant S195T bound with PPACK==		==Crystal structure of thrombin mutant S195T bound with PPACK==
	<StructureSection load='4rko' size='340' side='right' caption='[[4rko]], [[Resolution\|resolution]] 1.84Å' scene=''>		<StructureSection load='4rko' size='340' side='right' caption='[[4rko]], [[Resolution\|resolution]] 1.84Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4rkj\|4rkj]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4rkj\|4rkj]]</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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [http://www.ebi.ac.uk/pdbsum/4rko 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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [http://pdbe.org/4rko PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [http://www.ebi.ac.uk/pdbsum/4rko PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rko ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 21:
	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 4rko" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 11:50, 11 March 2015

OCA — Wed, 11 Mar 2015 11:50:42 GMT

←Older revision		Revision as of 11:50, 11 March 2015
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Crystal structure of thrombin mutant S195T bound with PPACK==
		+	<StructureSection load='4rko' size='340' side='right' caption='[[4rko]], [[Resolution\|resolution]] 1.84Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4rko]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RKO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RKO FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1shh\|1shh]], [[4rkj\|4rkj]]</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=4rko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rko OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rko RCSB], [http://www.ebi.ac.uk/pdbsum/4rko 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 ==
		+	Although Thr is equally represented as Ser in the human genome and as a nucleophile is as good as Ser, it is never found in the active site of the large family of trypsin-like proteases that utilize the Asp/His/Ser triad. The molecular basis of the preference of Ser over Thr in the trypsin fold was investigated with X-ray structures of the thrombin mutant S195T free and bound to an irreversible active site inhibitor. In the free form, the methyl group of T195 is oriented toward the incoming substrate in a conformation seemingly incompatible with productive binding. In the bound form, the side chain of T195 is reoriented for efficient substrate acylation without causing steric clash within the active site. Rapid kinetics prove that this change is due to selection of an active conformation from a preexisting ensemble of reactive and unreactive rotamers whose relative distribution determines the level of activity of the protease. Consistent with these observations, the S195T substitution is associated with a weak yet finite activity that allows identification of an unanticipated important role for S195 as the end point of allosteric transduction in the trypsin fold. The S195T mutation abrogates the Na(+)-dependent enhancement of catalytic activity in thrombin, activated protein C, and factor Xa and significantly weakens the physiologically important allosteric effects of thrombomodulin on thrombin and of cofactor Va on factor Xa. The evolutionary selection of Ser over Thr in trypsin-like proteases was therefore driven by the need for high catalytic activity and efficient allosteric regulation.

-	~~The entry 4rko is ON HOLD until Paper Publication~~	+	Why ser and not thr brokers catalysis in the trypsin fold.,Pelc LA, Chen Z, Gohara DW, Vogt AD, Pozzi N, Di Cera E Biochemistry. 2015 Feb 24;54(7):1457-64. doi: 10.1021/acs.biochem.5b00014. Epub, 2015 Feb 11. PMID:25664608<ref>PMID:25664608</ref>

-	~~Authors: Pelc~~, A.L.~~, Chen, Z., Gohara, D.W., Vogt, A.D., Pozzi, N., Di Cera, E~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Crystal structure of thrombin mutant S195T bound with PPACK~~	+	== References ==
-	[[Category: ~~Unreleased Structures~~]]	+	<references/>
-	[[Category: ~~Gohara~~, ~~D.W~~]]	+	__TOC__
-	[[Category: ~~Pelc~~, ~~A.L~~]]	+	</StructureSection>
-	[[Category: ~~Vogt~~, A.D]]	+	[[Category: Thrombin]]
-	[[Category: ~~Di Cera~~, E]]	+	[[Category: Cera, E Di]]
		+	[[Category: Chen, Z]]
		+	[[Category: Gohara, D W]]
		+	[[Category: Pelc, A L]]
	[[Category: Pozzi, N]]		[[Category: Pozzi, N]]
-	[[Category: ~~Chen~~, Z]]	+	[[Category: Vogt, A D]]
		+	[[Category: Allosteric regulation]]
		+	[[Category: Catalysis]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Trypsin-like protease]]

OCA at 16:59, 24 December 2014

OCA — Wed, 24 Dec 2014 16:59:22 GMT

←Older revision		Revision as of 16:59, 24 December 2014
Line 6:		Line 6:

	Description: Crystal structure of thrombin mutant S195T bound with PPACK		Description: Crystal structure of thrombin mutant S195T bound with PPACK
		+	[[Category: Unreleased Structures]]
		+	[[Category: Gohara, D.W]]
		+	[[Category: Pelc, A.L]]
		+	[[Category: Vogt, A.D]]
		+	[[Category: Di Cera, E]]
		+	[[Category: Pozzi, N]]
		+	[[Category: Chen, Z]]

OCA at 09:28, 24 December 2014

OCA — Wed, 24 Dec 2014 09:28:57 GMT

←Older revision		Revision as of 09:28, 24 December 2014
Line 3:		Line 3:
	The entry 4rko is ON HOLD until Paper Publication		The entry 4rko is ON HOLD until Paper Publication

-	Authors: Pelc, A.L., Chen, Z., Gohara, D.W., Vogt, A.D., Di Cera, E.	+	Authors: Pelc, A.L., Chen, Z., Gohara, D.W., Vogt, A.D., Pozzi, N., Di Cera, E.

	Description: Crystal structure of thrombin mutant S195T bound with PPACK		Description: Crystal structure of thrombin mutant S195T bound with PPACK

OCA at 11:26, 19 November 2014

OCA — Wed, 19 Nov 2014 11:26:46 GMT

←Older revision		Revision as of 11:26, 19 November 2014
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors: Pelc, A.L., Chen, Z., Gohara, D.W., Vogt, A.D., Di Cera, E.		Authors: Pelc, A.L., Chen, Z., Gohara, D.W., Vogt, A.D., Di Cera, E.

	Description: Crystal structure of thrombin mutant S195T bound with PPACK		Description: Crystal structure of thrombin mutant S195T bound with PPACK

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

OCA — Wed, 22 Oct 2014 09:45:07 GMT

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

←Older revision

Revision as of 09:45, 22 October 2014

OCA: New page: '''Unreleased structure''' The entry 4rko is ON HOLD Authors: Pelc, A.L., Chen, Z., Gohara, D.W., Vogt, A.D., Di Cera, E. Description: Crystal structure of thrombin mutant S195T bound ...

OCA — Wed, 22 Oct 2014 09:45:06 GMT

New page: '''Unreleased structure''' The entry 4rko is ON HOLD Authors: Pelc, A.L., Chen, Z., Gohara, D.W., Vogt, A.D., Di Cera, E. Description: Crystal structure of thrombin mutant S195T bound ...

New page

'''Unreleased structure'''

The entry 4rko is ON HOLD

Authors: Pelc, A.L., Chen, Z., Gohara, D.W., Vogt, A.D., Di Cera, E.

Description: Crystal structure of thrombin mutant S195T bound with PPACK