1dwc - Revision history

OCA at 09:54, 20 March 2024

2024-03-20T09:54:46Z

←Older revision		Revision as of 09:54, 20 March 2024
Line 3:		Line 3:
	<StructureSection load='1dwc' size='340' side='right'caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='1dwc' size='340' side='right'caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DWC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DWC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</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]] 3Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene></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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [https://pdbe.org/1dwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [https://www.ebi.ac.uk/pdbsum/1dwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dwc 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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [https://pdbe.org/1dwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [https://www.ebi.ac.uk/pdbsum/1dwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dwc 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/HIR3P_HIRME HIR3P_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 23:		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=1dwc 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=1dwc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The mode of binding of four active-site directed inhibitors to human thrombin has been determined by x-ray crystallographic analysis. The inhibitors studied are benzamidine, PPACK, NAPAP, and MD-805, of which the last three are compounds evolved specifically to inhibit thrombin. Crystal structures were determined in the presence of both the inhibitor and the undecapeptide [des-amino Asp55]hirudin(55-65) which binds distant from the active site. Despite having significantly different chemical structures, NAPAP and MD-805 bind to thrombin in a very similar "inhibitor binding mode" which is not that expected by direct analogy with the binding of substrate. Both inhibitors bind to thrombin in a similar way as to trypsin, but thrombin has an extra loop, the "Tyr-Pro-Pro-Trp loop," not present in trypsin, which gives further binding interactions and is seen to move somewhat to accommodate binding of the different inhibitors. The fact that NAPAP and MD-805 require different stereochemistry for potent inhibition is demonstrated, and its structural basis clarified. The wealth of data on analogs and variants of these lead compounds is shown to be compatible with this inhibitor binding mode.
-
-	Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors.,Banner DW, Hadvary P J Biol Chem. 1991 Oct 25;266(30):20085-93. PMID:1939071<ref>PMID:1939071</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1dwc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 40:		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: Banner DW]]
-	[[Category: Banner~~, D W~~]]	+	[[Category: Hadvary P]]
-	[[Category: Hadvary, P]]	+
-	~~[[Category: Hydrolase-hyrolase inhibitor complex]]~~	+
-	~~[[Category: Serine proteinase~~]]	+

OCA at 09:32, 21 July 2021

2021-07-21T09:32:10Z

←Older revision		Revision as of 09:32, 21 July 2021
Line 3:		Line 3:
	<StructureSection load='1dwc' size='340' side='right'caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='1dwc' size='340' side='right'caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1DWC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DWC FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [~~http~~://pdbe.org/1dwc PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1dwc PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1dwc 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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [https://pdbe.org/1dwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [https://www.ebi.ac.uk/pdbsum/1dwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dwc 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/HIR3P_HIRME HIR3P_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/HIR3P_HIRME HIR3P_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 3D structures\|Hirudin 3D structures]]		*[[Hirudin 3D structures\|Hirudin 3D structures]]
-	*[[Thrombin\|Thrombin]]	+	*[[Thrombin 3D Structures\|Thrombin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 10:39, 16 October 2019

2019-10-16T10:39:47Z

←Older revision		Revision as of 10:39, 16 October 2019
Line 1:		Line 1:

	==CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS==		==CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS==
-	<StructureSection load='1dwc' size='340' side='right' caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='1dwc' size='340' side='right'caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DWC FirstGlance]. <br>		<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DWC FirstGlance]. <br>
Line 32:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 1dwc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1dwc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hirudin 3D structures\|Hirudin 3D structures]]
		+	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>
Line 38:		Line 42:
	[[Category: Hirme]]		[[Category: Hirme]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Banner, D W]]		[[Category: Banner, D W]]

OCA at 07:58, 13 December 2017

2017-12-13T07:58:50Z

←Older revision		Revision as of 07:58, 13 December 2017
Line 1:		Line 1:
		+
	==CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS==		==CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS==
	<StructureSection load='1dwc' size='340' side='right' caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='1dwc' size='340' side='right' caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [http://pdbe.org/1dwc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [http://www.ebi.ac.uk/pdbsum/1dwc 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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [http://pdbe.org/1dwc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [http://www.ebi.ac.uk/pdbsum/1dwc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1dwc ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 16:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dw/1dwc_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dw/1dwc_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 31:		Line 32:
	</div>		</div>
	<div class="pdbe-citations 1dwc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1dwc" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Hirudin\|Hirudin]]
-	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 02:18, 7 February 2016

2016-02-07T02:18:21Z

←Older revision		Revision as of 02:18, 7 February 2016
Line 20:		Line 20:
	<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=1dwc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 20:44, 9 September 2015

2015-09-09T20:44:20Z

←Older revision		Revision as of 20:44, 9 September 2015
Line 2:		Line 2:
	<StructureSection load='1dwc' size='340' side='right' caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='1dwc' size='340' side='right' caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DWC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DWC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [http://www.ebi.ac.uk/pdbsum/1dwc 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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [http://pdbe.org/1dwc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [http://www.ebi.ac.uk/pdbsum/1dwc PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 30:		Line 30:
	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 1dwc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 38:		Line 39:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hirudo medicinalis~~]]	+	[[Category: Hirme]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Banner, D W]]		[[Category: Banner, D W]]

OCA at 18:27, 22 December 2014

2014-12-22T18:27:37Z

←Older revision		Revision as of 18:27, 22 December 2014
Line 3:		Line 3:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DWC FirstGlance]. <br>		<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DWC FirstGlance]. <br>
-	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene><br>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene></td></tr>
-	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [http://www.ebi.ac.uk/pdbsum/1dwc 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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [http://www.ebi.ac.uk/pdbsum/1dwc 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 41:		Line 41:
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
-	[[Category: Banner, D W.]]	+	[[Category: Banner, D W]]
-	[[Category: Hadvary, P.]]	+	[[Category: Hadvary, P]]
	[[Category: Hydrolase-hyrolase inhibitor complex]]		[[Category: Hydrolase-hyrolase inhibitor complex]]
	[[Category: Serine proteinase]]		[[Category: Serine proteinase]]

OCA at 13:59, 29 September 2014

2014-09-29T13:59:30Z

←Older revision		Revision as of 13:59, 29 September 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_1dwc\| PDB=1dwc \| SCENE= }}~~	+	==CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS==
-	===CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS===	+	<StructureSection load='1dwc' size='340' side='right' caption='[[1dwc]], [[Resolution\|resolution]] 3.00Å' scene=''>
-	{{~~ABSTRACT_PUBMED_1939071~~}}	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1dwc]] 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=1DWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1DWC FirstGlance]. <br>
		+	</td></tr><tr><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MIT:AMINO{[(4S)-5-[(2R,4R)-2-CARBOXY-4-METHYLPIPERIDIN-1-YL]-4-({[(3R)-3-METHYL-1,2,3,4-TETRAHYDROQUINOLIN-8-YL]SULFONYL}AMINO)-5-OXOPENTYL]AMINO}METHANIMINIUM'>MIT</scene><br>
		+	<tr><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1dwb\|1dwb]], [[1dwd\|1dwd]], [[1dwe\|1dwe]]</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=1dwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dwc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1dwc RCSB], [http://www.ebi.ac.uk/pdbsum/1dwc 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/HIR3P_HIRME HIR3P_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/dw/1dwc_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 mode of binding of four active-site directed inhibitors to human thrombin has been determined by x-ray crystallographic analysis. The inhibitors studied are benzamidine, PPACK, NAPAP, and MD-805, of which the last three are compounds evolved specifically to inhibit thrombin. Crystal structures were determined in the presence of both the inhibitor and the undecapeptide [des-amino Asp55]hirudin(55-65) which binds distant from the active site. Despite having significantly different chemical structures, NAPAP and MD-805 bind to thrombin in a very similar "inhibitor binding mode" which is not that expected by direct analogy with the binding of substrate. Both inhibitors bind to thrombin in a similar way as to trypsin, but thrombin has an extra loop, the "Tyr-Pro-Pro-Trp loop," not present in trypsin, which gives further binding interactions and is seen to move somewhat to accommodate binding of the different inhibitors. The fact that NAPAP and MD-805 require different stereochemistry for potent inhibition is demonstrated, and its structural basis clarified. The wealth of data on analogs and variants of these lead compounds is shown to be compatible with this inhibitor binding mode.

-	~~==Disease==~~	+	Crystallographic analysis at 3.0-A resolution of the binding to human thrombin of four active site-directed inhibitors.,Banner DW, Hadvary P J Biol Chem. 1991 Oct 25;266(30):20085-93. PMID:1939071<ref>PMID:1939071</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/HIR3P_HIRME HIR3P_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==~~	+
-	[[1dwc]] 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=1DWC OCA].	+

	==See Also==		==See Also==
	*[[Hirudin\|Hirudin]]		*[[Hirudin\|Hirudin]]
	*[[Thrombin\|Thrombin]]		*[[Thrombin\|Thrombin]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:001939071</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 09:20, 24 March 2013

2013-03-24T09:20:16Z

←Older revision		Revision as of 09:20, 24 March 2013
Line 1:		Line 1:
-	[[Image:1dwc.png\|left\|200px]]
-
	{{STRUCTURE_1dwc\| PDB=1dwc \| SCENE= }}		{{STRUCTURE_1dwc\| PDB=1dwc \| SCENE= }}
-
	===CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS===		===CRYSTALLOGRAPHIC ANALYSIS AT 3.0-ANGSTROMS RESOLUTION OF THE BINDING TO HUMAN THROMBIN OF FOUR ACTIVE SITE-DIRECTED INHIBITORS===
		+	{{ABSTRACT_PUBMED_1939071}}

-	~~{{ABSTRACT_PUBMED_1939071}}~~	+	==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/HIR3P_HIRME HIR3P_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 15:		Line 17:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:001939071</ref><references group="xtra"/>	+	<ref group="xtra">PMID:001939071</ref><references group="xtra"/><references/>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 05:19, 20 October 2012

2012-10-20T05:19:31Z

←Older revision		Revision as of 05:19, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1dwc]] 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=1DWC OCA].	+	[[1dwc]] 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=1DWC OCA].

	==See Also==		==See Also==
Line 15:		Line 15:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:001939071</ref><ref group="xtra">PMID:002226434</ref><ref group="xtra">PMID:002583108</ref><ref group="xtra">PMID:001304349</ref><ref group="xtra">PMID:002374926</ref><ref group="xtra">PMID:001587268</ref><ref group="xtra">PMID:002369893</ref><ref group="xtra">PMID:010336380</ref><references group="xtra"/>	+	<ref group="xtra">PMID:001939071</ref><references group="xtra"/>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]