4ufd - Revision history

OCA at 12:29, 20 December 2023

2023-12-20T12:29:33Z

←Older revision		Revision as of 12:29, 20 December 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ufd]] 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=4UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UFD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ufd]] 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=4UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UFD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S49:(2S)-N-[(4-CARBAMIMIDOYLPHENYL)METHYL]-1-[(2R)-3-PHENYL-2-[(PHENYLMETHYL)SULFONYLAMINO]PROPANOYL]PYRROLIDINE-2-CARBOXAMIDE'>S49</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.429Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S49:(2S)-N-[(4-CARBAMIMIDOYLPHENYL)METHYL]-1-[(2R)-3-PHENYL-2-[(PHENYLMETHYL)SULFONYLAMINO]PROPANOYL]PYRROLIDINE-2-CARBOXAMIDE'>S49</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufd OCA], [https://pdbe.org/4ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ufd RCSB], [https://www.ebi.ac.uk/pdbsum/4ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ufd 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=4ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufd OCA], [https://pdbe.org/4ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ufd RCSB], [https://www.ebi.ac.uk/pdbsum/4ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ufd ProSAT]</span></td></tr>
	</table>		</table>

OCA at 08:21, 22 March 2023

2023-03-22T08:21:36Z

←Older revision		Revision as of 08:21, 22 March 2023
Line 3:		Line 3:
	<StructureSection load='4ufd' size='340' side='right'caption='[[4ufd]], [[Resolution\|resolution]] 1.43Å' scene=''>		<StructureSection load='4ufd' size='340' side='right'caption='[[4ufd]], [[Resolution\|resolution]] 1.43Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ufd]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UFD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4UFD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ufd]] 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=4UFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UFD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S49:(2S)-N-[(4-CARBAMIMIDOYLPHENYL)METHYL]-1-[(2R)-3-PHENYL-2-[(PHENYLMETHYL)SULFONYLAMINO]PROPANOYL]PYRROLIDINE-2-CARBOXAMIDE'>S49</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S49:(2S)-N-[(4-CARBAMIMIDOYLPHENYL)METHYL]-1-[(2R)-3-PHENYL-2-[(PHENYLMETHYL)SULFONYLAMINO]PROPANOYL]PYRROLIDINE-2-CARBOXAMIDE'>S49</scene>, <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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufd OCA], [https://pdbe.org/4ufd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ufd RCSB], [https://www.ebi.ac.uk/pdbsum/4ufd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ufd ProSAT]</span></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ufe\|4ufe]], [[4uff\|4uff]], [[4ufg\|4ufg]]</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=4ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufd OCA], [~~http~~://pdbe.org/4ufd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ufd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ufd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ufd 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/HIRV2_HIRME HIRV2_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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 25:		Line 22:

	==See Also==		==See Also==
-	*[[Hirudin\|Hirudin]]	+	*[[Hirudin 3D structures\|Hirudin 3D structures]]
-	*[[Thrombin\|Thrombin]]	+	*[[Thrombin 3D Structures\|Thrombin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Thrombin]]~~	+	[[Category: Heine A]]
-	[[Category: Heine, A]]	+	[[Category: Klebe G]]
-	[[Category: Klebe, G]]	+	[[Category: Ruehmann E]]
-	[[Category: Ruehmann, E]]	+
-	~~[[Category: Blood]]~~	+
-	~~[[Category: Blood clotting]]~~	+
-	~~[[Category: Blood clotting inhibitor]]~~	+
-	~~[[Category: Blood coagulation]]~~	+
-	~~[[Category: Convertion of fibrinogen to fibrin]]~~	+
-	~~[[Category: Glycosylation]]~~	+
-	~~[[Category: Hydrolase]]~~	+
-	~~[[Category: Hydrolase inhibitor complex]]~~	+
-	~~[[Category: Preorganization]]~~	+
-	~~[[Category: Serine protease]]~~	+
-	~~[[Category: Thrombin inhibitor~~]]	+

OCA at 08:45, 21 May 2019

2019-05-21T08:45:58Z

←Older revision		Revision as of 08:45, 21 May 2019
Line 1:		Line 1:

	==Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)- 3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine==		==Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)- 3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine==
-	<StructureSection load='4ufd' size='340' side='right' caption='[[4ufd]], [[Resolution\|resolution]] 1.43Å' scene=''>	+	<StructureSection load='4ufd' size='340' side='right'caption='[[4ufd]], [[Resolution\|resolution]] 1.43Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ufd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UFD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UFD FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ufd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UFD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UFD FirstGlance]. <br>
Line 8:		Line 8:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ufe\|4ufe]], [[4uff\|4uff]], [[4ufg\|4ufg]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ufe\|4ufe]], [[4uff\|4uff]], [[4ufg\|4ufg]]</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=4ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufd OCA], [http://pdbe.org/4ufd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ufd RCSB], [http://www.ebi.ac.uk/pdbsum/4ufd 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=4ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufd OCA], [http://pdbe.org/4ufd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ufd RCSB], [http://www.ebi.ac.uk/pdbsum/4ufd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ufd ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 23:		Line 23:
	</div>		</div>
	<div class="pdbe-citations 4ufd" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4ufd" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hirudin\|Hirudin]]
		+	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>
Line 28:		Line 32:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Heine, A]]		[[Category: Heine, A]]

OCA at 07:08, 2 March 2016

2016-03-02T07:08:25Z

←Older revision		Revision as of 07:08, 2 March 2016
Line 1:		Line 1:
		+
	==Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)- 3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine==		==Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)- 3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine==
	<StructureSection load='4ufd' size='340' side='right' caption='[[4ufd]], [[Resolution\|resolution]] 1.43Å' scene=''>		<StructureSection load='4ufd' size='340' side='right' caption='[[4ufd]], [[Resolution\|resolution]] 1.43Å' scene=''>

OCA at 02:15, 28 January 2016

2016-01-28T02:15:58Z

←Older revision		Revision as of 02:15, 28 January 2016
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	==Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)- 3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine==
		+	<StructureSection load='4ufd' size='340' side='right' caption='[[4ufd]], [[Resolution\|resolution]] 1.43Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4ufd]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UFD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UFD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=S49:(2S)-N-[(4-CARBAMIMIDOYLPHENYL)METHYL]-1-[(2R)-3-PHENYL-2-[(PHENYLMETHYL)SULFONYLAMINO]PROPANOYL]PYRROLIDINE-2-CARBOXAMIDE'>S49</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">[[4ufe\|4ufe]], [[4uff\|4uff]], [[4ufg\|4ufg]]</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=4ufd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ufd OCA], [http://pdbe.org/4ufd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ufd RCSB], [http://www.ebi.ac.uk/pdbsum/4ufd 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/HIRV2_HIRME HIRV2_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 style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Structural preorganization to fix bioactive conformations at protein binding sites is a popular strategy to enhance binding affinity during late-stage optimization. The rationale for this enhancement relates to entropic advantages assigned to rigidified versus flexible ligands. We analyzed a narrow series of peptidomimetics binding to thrombin. The individual ligands exhibit at P2 a conformationally flexible glycine, more restricted alanine, N-methylglycine, N-methylhomoalanine, and largely rigidified proline moiety. Overall, affinity was found to increase by a factor of 1000, explained partly by an entropic advantage. All ligands adopt the same binding mode with small deviations. The residual mobility of the bound ligands is decreased across the series, and a protein side chain differs in its order/disorder behavior along with changes in the surface-water network pattern established across the newly generated protein-ligand surfaces. The enthalpy/entropy inventory displays a rather complex picture and emphasizes that thermodynamics can only be compared in terms of relative differences within a structurally similar ligand series.

-	~~The entry 4ufd is ON HOLD until Paper Publication~~	+	Boosting Affinity by Correct Ligand Preorganization for the S2 Pocket of Thrombin: A Study by Isothermal Titration Calorimetry, Molecular Dynamics, and High-Resolution Crystal Structures.,Ruhmann EH, Rupp M, Betz M, Heine A, Klebe G ChemMedChem. 2016 Jan 13. doi: 10.1002/cmdc.201500531. PMID:26762840<ref>PMID:26762840</ref>

-	~~Authors: Ruehmann~~, E.~~, Heine, A~~.~~, Klebe, G~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~Description: Thrombin in complex with 4~~-~~(((1~~-~~((2S)-1-((2R)-2-(benzylsulfonylamino)-3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine~~	+	<div class="pdbe-citations 4ufd" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Unreleased Structures~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Thrombin]]
	[[Category: Heine, A]]		[[Category: Heine, A]]
		+	[[Category: Klebe, G]]
	[[Category: Ruehmann, E]]		[[Category: Ruehmann, E]]
-	[[Category: ~~Klebe, G~~]]	+	[[Category: Blood]]
		+	[[Category: Blood clotting]]
		+	[[Category: Blood clotting inhibitor]]
		+	[[Category: Blood coagulation]]
		+	[[Category: Convertion of fibrinogen to fibrin]]
		+	[[Category: Glycosylation]]
		+	[[Category: Hydrolase]]
		+	[[Category: Hydrolase inhibitor complex]]
		+	[[Category: Preorganization]]
		+	[[Category: Serine protease]]
		+	[[Category: Thrombin inhibitor]]

OCA at 22:56, 30 November 2015

2015-11-30T22:56:53Z

←Older revision		Revision as of 22:56, 30 November 2015
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	Description: Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)-3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine		Description: Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)-3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
		+	[[Category: Heine, A]]
	[[Category: Ruehmann, E]]		[[Category: Ruehmann, E]]
	[[Category: Klebe, G]]		[[Category: Klebe, G]]
-	[[Category: Heine, A]]

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

2015-03-26T10:37:36Z

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

←Older revision

Revision as of 10:37, 26 March 2015

OCA: New page: '''Unreleased structure''' The entry 4ufd is ON HOLD until Paper Publication Authors: Ruehmann, E., Heine, A., Klebe, G. Description: Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(b...

2015-03-26T10:37:35Z

New page: '''Unreleased structure''' The entry 4ufd is ON HOLD until Paper Publication Authors: Ruehmann, E., Heine, A., Klebe, G. Description: Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(b...

New page

'''Unreleased structure'''

The entry 4ufd is ON HOLD until Paper Publication

Authors: Ruehmann, E., Heine, A., Klebe, G.

Description: Thrombin in complex with 4-(((1-((2S)-1-((2R)-2-(benzylsulfonylamino)-3-phenyl-propanoyl)pyrrolidin-2-yl)-1-oxo-ethyl)amino)methyl) benzamidine
[[Category: Unreleased Structures]]
[[Category: Ruehmann, E]]
[[Category: Klebe, G]]
[[Category: Heine, A]]