1kts - Revision history

OCA at 08:03, 3 April 2024

2024-04-03T08:03:42Z

←Older revision		Revision as of 08:03, 3 April 2024
Line 3:		Line 3:
	<StructureSection load='1kts' size='340' side='right'caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='1kts' size='340' side='right'caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Hirme Hirme~~] and [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KTS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KTS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</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]] 2.4Å</td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene~~></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</div></td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [https://pdbe.org/1kts PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [https://www.ebi.ac.uk/pdbsum/1kts PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kts 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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [https://pdbe.org/1kts PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [https://www.ebi.ac.uk/pdbsum/1kts PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kts ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[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>	+	[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 ==
-	[[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> [[https://www.uniprot.org/uniprot/HIR2B_HIRME HIR2B_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.	+	[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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 24:		Line 22:
	</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=1kts 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=1kts ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The clinical syndromes of thromboembolism are evoked by an excessive stimulation of the coagulation cascade. In this context, the serine protease thrombin plays a key role. Considerable efforts have therefore been devoted to the discovery of safe, orally active inhibitors of this enzyme. On the basis of the X-ray crystal structure of the peptide-like thrombin inhibitor NAPAP complexed with bovine thrombin, we have designed a new structural class of nonpeptidic inhibitors employing a 1,2,5-trisubstituted benzimidazole as the central scaffold. Supported by a series of X-ray structure analyses, we optimized the activity of these compounds. Thrombin inhibition in the lower nanomolar range could be achieved although the binding energy mainly results from nonpolar, hydrophobic interactions. To improve in vivo potency, we increased the overall hydrophilicity of the molecules by introducing carboxylate groups. The very polar compound 24 (BIBR 953) exhibited the most favorable activity profile in vivo. This zwitterionic molecule was converted into the double-prodrug 31 (BIBR 1048), which showed strong oral activity in different animal species. On the basis of these results, 31 was chosen for clinical development.
-
-	Structure-based design of novel potent nonpeptide thrombin inhibitors.,Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W J Med Chem. 2002 Apr 25;45(9):1757-66. PMID:11960487<ref>PMID:11960487</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1kts" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 41:		Line 30:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hirme~~]]	+	[[Category: Hirudo medicinalis]]
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Thrombin]]~~	+	[[Category: Nar H]]
-	[[Category: Nar, H]]	+
-	~~[[Category: Blood clotting]]~~	+
-	~~[[Category: Blood coagulation]]~~	+
-	~~[[Category: Hydrolase-hydrolase inhibitor complex]]~~	+
-	~~[[Category: Inhibition~~]]	+

OCA at 08:50, 21 April 2021

2021-04-21T08:50:27Z

←Older revision		Revision as of 08:50, 21 April 2021
Line 3:		Line 3:
	<StructureSection load='1kts' size='340' side='right'caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='1kts' size='340' side='right'caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Hirme Hirme] and [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1KTS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Hirme Hirme] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1KTS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</div></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'>[https://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [https://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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [~~http~~://pdbe.org/1kts PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1kts PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1kts 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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [https://pdbe.org/1kts PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [https://www.ebi.ac.uk/pdbsum/1kts PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1kts 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> [[~~http~~://www.uniprot.org/uniprot/HIR2B_HIRME HIR2B_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.	+	[[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> [[https://www.uniprot.org/uniprot/HIR2B_HIRME HIR2B_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 35:		Line 35:

	==See Also==		==See Also==
-	*[[Hirudin\|Hirudin]]	+	*[[Hirudin 3D structures\|Hirudin 3D structures]]
-	*[[Thrombin\|Thrombin]]	+	*[[Thrombin 3D Structures\|Thrombin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 13:16, 17 July 2019

2019-07-17T13:16:40Z

←Older revision		Revision as of 13:16, 17 July 2019
Line 1:		Line 1:

	==Thrombin Inhibitor Complex==		==Thrombin Inhibitor Complex==
-	<StructureSection load='1kts' size='340' side='right' caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>	+	<StructureSection load='1kts' size='340' side='right'caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirme Hirme] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KTS FirstGlance]. <br>		<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirme Hirme] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KTS FirstGlance]. <br>
Line 18:		Line 18:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kt/1kts_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kt/1kts_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>
Line 33:		Line 33:
	</div>		</div>
	<div class="pdbe-citations 1kts" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1kts" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hirudin\|Hirudin]]
		+	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>
Line 39:		Line 43:
	[[Category: Hirme]]		[[Category: Hirme]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Nar, H]]		[[Category: Nar, H]]

OCA at 07:31, 11 October 2017

2017-10-11T07:31:14Z

←Older revision		Revision as of 07:31, 11 October 2017
Line 1:		Line 1:
		+
	==Thrombin Inhibitor Complex==		==Thrombin Inhibitor Complex==
	<StructureSection load='1kts' size='340' side='right' caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>		<StructureSection load='1kts' size='340' side='right' caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Hirudo_medicinalis Hirudo medicinalis~~] and [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KTS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirme Hirme] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KTS FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [http://pdbe.org/1kts PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [http://www.ebi.ac.uk/pdbsum/1kts 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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [http://pdbe.org/1kts PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [http://www.ebi.ac.uk/pdbsum/1kts PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1kts ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	<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=1kts ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 32:		Line 33:
	</div>		</div>
	<div class="pdbe-citations 1kts" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1kts" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Hirudin\|Hirudin]]
-	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hirudo medicinalis~~]]	+	[[Category: Hirme]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Nar, H]]		[[Category: Nar, H]]

OCA at 10:41, 11 September 2015

2015-09-11T10:41:37Z

←Older revision		Revision as of 10:41, 11 September 2015
Line 7:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [http://www.ebi.ac.uk/pdbsum/1kts 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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [http://pdbe.org/1kts PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [http://www.ebi.ac.uk/pdbsum/1kts PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		Line 31:
	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 1kts" style="background-color:#fffaf0;"></div>

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

OCA at 15:43, 5 January 2015

2015-01-05T15:43:29Z

←Older revision		Revision as of 15:43, 5 January 2015
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KTS FirstGlance]. <br>		<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KTS FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [http://www.ebi.ac.uk/pdbsum/1kts 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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [http://www.ebi.ac.uk/pdbsum/1kts 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 42:		Line 42:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
-	[[Category: Nar, H.]]	+	[[Category: Nar, H]]
	[[Category: Blood clotting]]		[[Category: Blood clotting]]
	[[Category: Blood coagulation]]		[[Category: Blood coagulation]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Inhibition]]		[[Category: Inhibition]]

OCA at 14:04, 29 September 2014

2014-09-29T14:04:04Z

←Older revision		Revision as of 14:04, 29 September 2014
Line 1:		Line 1:
-	{~~{STRUCTURE_1kts~~\| ~~PDB~~=1kts \| ~~SCENE~~= }}	+	==Thrombin Inhibitor Complex==
-	===~~Thrombin Inhibitor Complex~~===	+	<StructureSection load='1kts' size='340' side='right' caption='[[1kts]], [[Resolution\|resolution]] 2.40Å' scene=''>
-	~~{{ABSTRACT_PUBMED_11960487}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KTS FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C24:3-({2-[(4-CARBAMIMIDOYL-PHENYLAMINO)-METHYL]-3-METHYL-3H-BENZOIMIDAZOLE-5-CARBONYL}-PYRIDIN-2-YL-AMINO)-PROPIONIC+ACID+ETHYL+ESTER'>C24</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1ktt\|1ktt]], [[1g30\|1g30]], [[1g32\|1g32]]</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=1kts FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1kts OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1kts RCSB], [http://www.ebi.ac.uk/pdbsum/1kts 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> [[http://www.uniprot.org/uniprot/HIR2B_HIRME HIR2B_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.
		+	== 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/kt/1kts_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 ==
		+	The clinical syndromes of thromboembolism are evoked by an excessive stimulation of the coagulation cascade. In this context, the serine protease thrombin plays a key role. Considerable efforts have therefore been devoted to the discovery of safe, orally active inhibitors of this enzyme. On the basis of the X-ray crystal structure of the peptide-like thrombin inhibitor NAPAP complexed with bovine thrombin, we have designed a new structural class of nonpeptidic inhibitors employing a 1,2,5-trisubstituted benzimidazole as the central scaffold. Supported by a series of X-ray structure analyses, we optimized the activity of these compounds. Thrombin inhibition in the lower nanomolar range could be achieved although the binding energy mainly results from nonpolar, hydrophobic interactions. To improve in vivo potency, we increased the overall hydrophilicity of the molecules by introducing carboxylate groups. The very polar compound 24 (BIBR 953) exhibited the most favorable activity profile in vivo. This zwitterionic molecule was converted into the double-prodrug 31 (BIBR 1048), which showed strong oral activity in different animal species. On the basis of these results, 31 was chosen for clinical development.

-	~~==Disease==~~	+	Structure-based design of novel potent nonpeptide thrombin inhibitors.,Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W J Med Chem. 2002 Apr 25;45(9):1757-66. PMID:11960487<ref>PMID:11960487</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>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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~~> [[http://www.uniprot.org/uniprot/HIR2B_HIRME HIR2B_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA].	+

	==See Also==		==See Also==
	*[[Hirudin\|Hirudin]]		*[[Hirudin\|Hirudin]]
	*[[Thrombin\|Thrombin]]		*[[Thrombin\|Thrombin]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:011960487</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 09:34, 24 March 2013

2013-03-24T09:34:47Z

←Older revision		Revision as of 09:34, 24 March 2013
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	===Thrombin Inhibitor Complex===		===Thrombin Inhibitor Complex===
	{{ABSTRACT_PUBMED_11960487}}		{{ABSTRACT_PUBMED_11960487}}
		+
		+	==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> [[http://www.uniprot.org/uniprot/HIR2B_HIRME HIR2B_HIRME]] Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen.

	==About this Structure==		==About this Structure==
Line 11:		Line 17:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:011960487</ref><references group="xtra"/>	+	<ref group="xtra">PMID:011960487</ref><references group="xtra"/><references/>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 09:23, 13 March 2013

2013-03-13T09:23:51Z

←Older revision		Revision as of 09:23, 13 March 2013
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-	[[Image:1kts.png\|left\|200px]]
-
	{{STRUCTURE_1kts\| PDB=1kts \| SCENE= }}		{{STRUCTURE_1kts\| PDB=1kts \| SCENE= }}
-
	===Thrombin Inhibitor Complex===		===Thrombin Inhibitor Complex===
-
	{{ABSTRACT_PUBMED_11960487}}		{{ABSTRACT_PUBMED_11960487}}

OCA at 18:16, 20 October 2012

2012-10-20T18:16:13Z

←Older revision		Revision as of 18:16, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1kts]] is a 3 chain structure ~~of [[Hirudin]] and [[Thrombin]]~~ with sequence from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA].	+	[[1kts]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KTS OCA].

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