4htc - Revision history

OCA at 09:20, 5 February 2020

2020-02-05T09:20:35Z

←Older revision		Revision as of 09:20, 5 February 2020
Line 1:		Line 1:

	==THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX==		==THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX==
-	<StructureSection load='4htc' size='340' side='right' caption='[[4htc]], [[Resolution\|resolution]] 2.30Å' scene=''>	+	<StructureSection load='4htc' size='340' side='right'caption='[[4htc]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4htc]] 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=4HTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTC FirstGlance]. <br>		<table><tr><td colspan='2'>[[4htc]] 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=4HTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTC FirstGlance]. <br>
Line 16:		Line 16:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ht/4htc_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ht/4htc_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 31:
	</div>		</div>
	<div class="pdbe-citations 4htc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4htc" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Hirudin\|Hirudin]]
		+	*[[Hirudin 3D structures\|Hirudin 3D structures]]
		+	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>
Line 37:		Line 42:
	[[Category: Hirme]]		[[Category: Hirme]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Bode, W]]		[[Category: Bode, W]]

OCA at 07:20, 29 November 2017

2017-11-29T07:20:16Z

←Older revision		Revision as of 07:20, 29 November 2017
Line 1:		Line 1:
		+
	==THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX==		==THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX==
	<StructureSection load='4htc' size='340' side='right' caption='[[4htc]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4htc' size='340' side='right' caption='[[4htc]], [[Resolution\|resolution]] 2.30Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4htc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htc OCA], [http://pdbe.org/4htc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4htc RCSB], [http://www.ebi.ac.uk/pdbsum/4htc 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=4htc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htc OCA], [http://pdbe.org/4htc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4htc RCSB], [http://www.ebi.ac.uk/pdbsum/4htc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4htc ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 30:		Line 31:
	</div>		</div>
	<div class="pdbe-citations 4htc" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 4htc" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Hirudin\|Hirudin]]
-	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 17:53, 8 February 2016

2016-02-08T17:53:35Z

←Older revision		Revision as of 17:53, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='4htc' size='340' side='right' caption='[[4htc]], [[Resolution\|resolution]] 2.30Å' scene=''>		<StructureSection load='4htc' size='340' side='right' caption='[[4htc]], [[Resolution\|resolution]] 2.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4htc]] 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=4HTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTC FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4htc]] 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=4HTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTC FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4htc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4htc RCSB], [http://www.ebi.ac.uk/pdbsum/4htc 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=4htc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htc OCA], [http://pdbe.org/4htc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4htc RCSB], [http://www.ebi.ac.uk/pdbsum/4htc 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>
	== 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/~~ITH3_HIRME ITH3_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.	+	[[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.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	<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=4htc ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 29:		Line 29:
	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 4htc" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 37:		Line 38:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Hirudo medicinalis~~]]	+	[[Category: Hirme]]
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Bode, W]]		[[Category: Bode, W]]

OCA at 12:07, 21 December 2014

2014-12-21T12:07:19Z

←Older revision		Revision as of 12:07, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4htc~~\| ~~PDB~~=4htc \| ~~SCENE~~= }}	+	==THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX==
-	===~~THE REFINED STRUCTURE OF THE HIRUDIN~~-~~THROMBIN COMPLEX~~===	+	<StructureSection load='4htc' size='340' side='right' caption='[[4htc]], [[Resolution\|resolution]] 2.30Å' scene=''>
-	~~{{ABSTRACT_PUBMED_1920434}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4htc]] 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=4HTC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HTC FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=4htc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4htc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4htc RCSB], [http://www.ebi.ac.uk/pdbsum/4htc 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/ITH3_HIRME ITH3_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/ht/4htc_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 structure of a recombinant hirudin (variant 2, Lys47) human alpha-thrombin complex has been refined using restrained least-squares methods to a crystallographic R-factor of 0.173. The hirudin structure consists of an N-terminal domain folded into a globular unit and a long 17-peptide C-terminal in an extended chain conformation. The N-terminal domain binds at the active-site of thrombin where Ile1' to Tyr3' penetrates to the catalytic triad. The alpha-amino group of Ile1' of hirudin makes a hydrogen bond with OG of Ser195 of thrombin, the side-chains of Ile1' and Tyr3' occupy the apolar site, Thr2' is at the entrance to, but does not enter, the S1 specificity site and Ile1' to Tyr3' form a parallel beta-strand with Ser214 to Gly219. The latter interaction is antiparallel in all other serine proteinase-protein inhibitor complexes. The extended C-terminal segment of hirudin, which is abundant in acidic residues, makes many electrostatic interactions with the fibrinogen binding exosite while the last five residues are in a 3(10) helical turn residing in a hydrophobic patch on the thrombin surface. The precision of the complementarity displayed by these two molecules produces numerous interactions, which although independently generally weak, together are responsible for the high degree of affinity and specificity. Although hirudin-thrombin and D-Phe-Pro-Arg-chloromethyl ketone-thrombin differ in conformation in the autolysis loop (Lys145 to Gly150), this is most likely due to different crystal packing interactions and changes in circular dichroism between the two are probably due to the inherent flexibility of the loop. An RGD sequence, which is generally known to be involved in cell surface receptor interactions, occurs in thrombin and is associated with a long solvent channel filled with water molecules leading to the surface from the end of the S1 site. However, the RGD triplet does not appear to be able to interact in concert in a surface binding mode.

-	~~==Disease==~~	+	Refined structure of the hirudin-thrombin complex.,Rydel TJ, Tulinsky A, Bode W, Huber R J Mol Biol. 1991 Sep 20;221(2):583-601. PMID:1920434<ref>PMID:1920434</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/ITH3_HIRME ITH3_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==~~	+
-	[[4htc]] 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=4HTC OCA].	+

	==See Also==		==See Also==
	*[[Hirudin\|Hirudin]]		*[[Hirudin\|Hirudin]]
	*[[Thrombin\|Thrombin]]		*[[Thrombin\|Thrombin]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:001920434</ref><ref group="xtra">PMID:016673263</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
-	[[Category: Bode, W.]]	+	[[Category: Bode, W]]
-	[[Category: Huber, R.]]	+	[[Category: Huber, R]]
-	[[Category: Rydel, T J.]]	+	[[Category: Rydel, T J]]
-	[[Category: Tulinsky, A.]]	+	[[Category: Tulinsky, A]]
	[[Category: Hydrolase-hydrolase inhibitor complex]]		[[Category: Hydrolase-hydrolase inhibitor complex]]
	[[Category: Serine protease]]		[[Category: Serine protease]]

OCA at 19:21, 24 March 2013

2013-03-24T19:21:52Z

←Older revision		Revision as of 19:21, 24 March 2013
Line 1:		Line 1:
-	[[Image:4htc.png\|left\|200px]]
-
	{{STRUCTURE_4htc\| PDB=4htc \| SCENE= }}		{{STRUCTURE_4htc\| PDB=4htc \| SCENE= }}
-
	===THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX===		===THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX===
		+	{{ABSTRACT_PUBMED_1920434}}

-	~~{{ABSTRACT_PUBMED_1920434}}~~	+	==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/ITH3_HIRME ITH3_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:001920434</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/>	+	<ref group="xtra">PMID:001920434</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/><references/>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]

OCA at 10:58, 20 October 2012

2012-10-20T10:58:12Z

←Older revision		Revision as of 10:58, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[4htc]] 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=4HTC OCA].	+	[[4htc]] 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=4HTC OCA].

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

OCA at 03:50, 26 July 2012

2012-07-26T03:50:44Z

←Older revision		Revision as of 03:50, 26 July 2012
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	[[Image:4htc.png\|left\|200px]]		[[Image:4htc.png\|left\|200px]]

-	<!--
-	The line below this paragraph, containing "STRUCTURE_4htc", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_4htc\| PDB=4htc \| SCENE= }}		{{STRUCTURE_4htc\| PDB=4htc \| SCENE= }}

	===THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX===		===THE REFINED STRUCTURE OF THE HIRUDIN-THROMBIN COMPLEX===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_1920434}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 1920434 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_1920434}}		{{ABSTRACT_PUBMED_1920434}}

	==About this Structure==		==About this Structure==
-	[[4htc]] is a 3 chain structure of [[Hirudin]] 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=4HTC OCA].	+	[[4htc]] 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=4HTC OCA].

	==See Also==		==See Also==
-	*[[Hirudin]]	+	*[[Hirudin\|Hirudin]]
		+	*[[Thrombin\|Thrombin]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~1920434~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:001920434</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
Line 33:		Line 23:
	[[Category: Rydel, T J.]]		[[Category: Rydel, T J.]]
	[[Category: Tulinsky, A.]]		[[Category: Tulinsky, A.]]
		+	[[Category: Hydrolase-hydrolase inhibitor complex]]
		+	[[Category: Serine protease]]

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

2010-12-27T00:56:32Z

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

←Older revision

Revision as of 00:56, 27 December 2010

OCA at 00:56, 27 December 2010

2010-12-27T00:56:31Z

←Older revision		Revision as of 00:56, 27 December 2010
Line 1:		Line 1:
-	{{Seed}}
	[[Image:4htc.png\|left\|200px]]		[[Image:4htc.png\|left\|200px]]

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	==About this Structure==		==About this Structure==
-	~~4HTC~~ is a 3 ~~chains~~ structure of ~~sequences~~ 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=4HTC OCA].	+	[[4htc]] is a 3 chain structure of [[Hirudin]] 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=4HTC OCA].
		+
		+	==See Also==
		+	*[[Hirudin]]

	==Reference==		==Reference==
Line 31:		Line 33:
	[[Category: Rydel, T J.]]		[[Category: Rydel, T J.]]
	[[Category: Tulinsky, A.]]		[[Category: Tulinsky, A.]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 00:56:00 2009''

OCA at 22:56, 16 February 2009

2009-02-16T22:56:03Z

←Older revision		Revision as of 22:56, 16 February 2009
Line 20:		Line 20:

	==About this Structure==		==About this Structure==
-	4HTC is a ~~[[Protein complex]]~~ structure of sequences 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=4HTC OCA].	+	4HTC is a 3 chains structure of sequences 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=4HTC OCA].

	==Reference==		==Reference==
-	~~Refined structure of the hirudin-thrombin complex., Rydel TJ, Tulinsky A, Bode W, Huber R, J Mol Biol. 1991 Sep 20;221(2):583-601.~~ PMID:~~[http:~~//~~www.ncbi.nlm.nih.gov/pubmed/1920434 1920434]~~	+	<ref group="xtra">PMID:1920434</ref><references group="xtra"/>
	[[Category: Hirudo medicinalis]]		[[Category: Hirudo medicinalis]]
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Protein complex]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Bode, W.]]		[[Category: Bode, W.]]
Line 33:		Line 32:
	[[Category: Tulinsky, A.]]		[[Category: Tulinsky, A.]]

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Thu Jul 3 13~~:41:~~13 2008~~''	+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 00:56:00 2009''