4ch2 - Revision history

OCA at 12:10, 20 December 2023

2023-12-20T12:10:11Z

←Older revision		Revision as of 12:10, 20 December 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ch2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CH2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ch2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CH2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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]] 1.6Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=4ch2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ch2 OCA], [https://pdbe.org/4ch2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ch2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ch2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ch2 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=4ch2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ch2 OCA], [https://pdbe.org/4ch2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ch2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ch2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ch2 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/THRB_HUMAN THRB_HUMAN] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Activation of platelets by the serine protease thrombin is a critical event in haemostasis. This process involves the binding of thrombin to glycoprotein Ibalpha (GpIbalpha) and cleavage of protease-activated receptors (PARs). The N-terminal extracellular domain of GpIbalpha contains an acidic peptide stretch that has been identified as the main thrombin binding site, and both anion binding exosites of thrombin have been implicated in GpIbalpha binding, but it remains unclear how they are involved. This issue is of critical importance for the mechanism of platelet activation by thrombin. If both exosites bind to GpIbalpha, thrombin could potentially act as a platelet adhesion molecule or receptor dimerisation trigger. Alternatively, if only a single site is involved, GpIbalpha may serve as a cofactor for PAR-1 activation by thrombin. To determine the involvement of thrombin's two exosites in GpIbalpha binding, we employed the complementary methods of mutational analysis, binding studies, X-ray crystallography and NMR spectroscopy. Our results indicate that the peptide corresponding to the C-terminal portion of GpIbalpha and the entire extracellular domain bind exclusively to thrombin's exosite II. The interaction of thrombin with GpIbalpha thus serves to recruit thrombin activity to the platelet surface while leaving exosite I free for PAR-1 recognition.
		+
		+	GpIbalpha Interacts Exclusively with Exosite II of Thrombin.,Lechtenberg BC, Freund SM, Huntington JA J Mol Biol. 2013 Dec 5. pii: S0022-2836(13)00738-9. doi:, 10.1016/j.jmb.2013.11.027. PMID:24316004<ref>PMID:24316004</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 4ch2" style="background-color:#fffaf0;"></div>

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

OCA at 17:45, 7 September 2022

2022-09-07T17:45:48Z

←Older revision		Revision as of 17:45, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='4ch2' size='340' side='right'caption='[[4ch2]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4ch2' size='340' side='right'caption='[[4ch2]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4ch2]] is a 6 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4CH2 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4ch2]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CH2 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</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=4ch2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ch2 OCA], [https://pdbe.org/4ch2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ch2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ch2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ch2 ProSAT]</span></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ch8\|4ch8]]</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=4ch2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ch2 OCA], [~~http~~://pdbe.org/4ch2 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4ch2 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4ch2 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4ch2 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> [[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</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/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.	+	[[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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Activation of platelets by the serine protease thrombin is a critical event in haemostasis. This process involves the binding of thrombin to glycoprotein Ibalpha (GpIbalpha) and cleavage of protease-activated receptors (PARs). The N-terminal extracellular domain of GpIbalpha contains an acidic peptide stretch that has been identified as the main thrombin binding site, and both anion binding exosites of thrombin have been implicated in GpIbalpha binding, but it remains unclear how they are involved. This issue is of critical importance for the mechanism of platelet activation by thrombin. If both exosites bind to GpIbalpha, thrombin could potentially act as a platelet adhesion molecule or receptor dimerisation trigger. Alternatively, if only a single site is involved, GpIbalpha may serve as a cofactor for PAR-1 activation by thrombin. To determine the involvement of thrombin's two exosites in GpIbalpha binding, we employed the complementary methods of mutational analysis, binding studies, X-ray crystallography and NMR spectroscopy. Our results indicate that the peptide corresponding to the C-terminal portion of GpIbalpha and the entire extracellular domain bind exclusively to thrombin's exosite II. The interaction of thrombin with GpIbalpha thus serves to recruit thrombin activity to the platelet surface while leaving exosite I free for PAR-1 recognition.	+
-		+
-	GpIbalpha Interacts Exclusively with Exosite II of Thrombin.,Lechtenberg BC, Freund SM, Huntington JA J Mol Biol. 2013 Dec 5. pii: S0022-2836(13)00738-9. doi:, 10.1016/j.jmb.2013.11.027. PMID:24316004<ref>PMID:24316004</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4ch2" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
-	*[[Thrombin\|Thrombin]]	+	*[[Thrombin 3D Structures\|Thrombin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Thrombin]]~~	+	[[Category: Freund SMV]]
-	[[Category: Freund~~, S M.V~~]]	+	[[Category: Huntington JA]]
-	[[Category: Huntington~~, J A~~]]	+	[[Category: Lechtenberg BC]]
-	[[Category: Lechtenberg~~, B C]]~~	+
-	~~[[Category: Hydrolase-peptide complex~~]]	+

OCA at 10:00, 20 March 2019

2019-03-20T10:00:32Z

←Older revision		Revision as of 10:00, 20 March 2019
Line 1:		Line 1:

	==Low-salt crystal structure of a thrombin-GpIbalpha peptide complex==		==Low-salt crystal structure of a thrombin-GpIbalpha peptide complex==
-	<StructureSection load='4ch2' size='340' side='right' caption='[[4ch2]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='4ch2' size='340' side='right'caption='[[4ch2]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4ch2]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CH2 FirstGlance]. <br>		<table><tr><td colspan='2'>[[4ch2]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CH2 FirstGlance]. <br>
Line 31:		Line 31:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Freund, S M.V]]		[[Category: Freund, S M.V]]

OCA at 23:31, 5 August 2016

2016-08-05T23:31:05Z

←Older revision		Revision as of 23:31, 5 August 2016
Line 1:		Line 1:
		+
	==Low-salt crystal structure of a thrombin-GpIbalpha peptide complex==		==Low-salt crystal structure of a thrombin-GpIbalpha peptide complex==
	<StructureSection load='4ch2' size='340' side='right' caption='[[4ch2]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='4ch2' size='340' side='right' caption='[[4ch2]], [[Resolution\|resolution]] 1.60Å' scene=''>
Line 7:		Line 8:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ch8\|4ch8]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ch8\|4ch8]]</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=4ch2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ch2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ch2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ch2 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=4ch2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ch2 OCA], [http://pdbe.org/4ch2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ch2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ch2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ch2 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	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 4ch2" style="background-color:#fffaf0;"></div>

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

OCA at 18:58, 21 December 2014

2014-12-21T18:58:30Z

←Older revision		Revision as of 18:58, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4ch2\| PDB=4ch2 \| SCENE= }}~~	+	==Low-salt crystal structure of a thrombin-GpIbalpha peptide complex==
-	===Low-salt crystal structure of a thrombin-GpIbalpha peptide complex===	+	<StructureSection load='4ch2' size='340' side='right' caption='[[4ch2]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	{~~{ABSTRACT_PUBMED_24316004}~~}	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4ch2]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CH2 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0G6:D-PHENYLALANYL-N-[(2S,3S)-6-{[AMINO(IMINIO)METHYL]AMINO}-1-CHLORO-2-HYDROXYHEXAN-3-YL]-L-PROLINAMIDE'>0G6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ch8\|4ch8]]</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=4ch2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ch2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ch2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ch2 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> [[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</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> [[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</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/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Activation of platelets by the serine protease thrombin is a critical event in haemostasis. This process involves the binding of thrombin to glycoprotein Ibalpha (GpIbalpha) and cleavage of protease-activated receptors (PARs). The N-terminal extracellular domain of GpIbalpha contains an acidic peptide stretch that has been identified as the main thrombin binding site, and both anion binding exosites of thrombin have been implicated in GpIbalpha binding, but it remains unclear how they are involved. This issue is of critical importance for the mechanism of platelet activation by thrombin. If both exosites bind to GpIbalpha, thrombin could potentially act as a platelet adhesion molecule or receptor dimerisation trigger. Alternatively, if only a single site is involved, GpIbalpha may serve as a cofactor for PAR-1 activation by thrombin. To determine the involvement of thrombin's two exosites in GpIbalpha binding, we employed the complementary methods of mutational analysis, binding studies, X-ray crystallography and NMR spectroscopy. Our results indicate that the peptide corresponding to the C-terminal portion of GpIbalpha and the entire extracellular domain bind exclusively to thrombin's exosite II. The interaction of thrombin with GpIbalpha thus serves to recruit thrombin activity to the platelet surface while leaving exosite I free for PAR-1 recognition.

-	~~==Function==~~	+	GpIbalpha Interacts Exclusively with Exosite II of Thrombin.,Lechtenberg BC, Freund SM, Huntington JA J Mol Biol. 2013 Dec 5. pii: S0022-2836(13)00738-9. doi:, 10.1016/j.jmb.2013.11.027. PMID:24316004<ref>PMID:24316004</ref>
-	~~[[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/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.	+

-	~~==About this Structure==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[4ch2]] is~~ a ~~6 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.~~ac.il~~/~~oca-bin/ocashort?id=4CH2 OCA].~~	+	</div>

-	==~~Reference~~==	+	==See Also==
-	~~<ref group~~=~~"xtra">PMID:024316004</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	*[[Thrombin\|Thrombin]]
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
-	[[Category: Freund, S M.V.]]	+	[[Category: Freund, S M.V]]
-	[[Category: Huntington, J A.]]	+	[[Category: Huntington, J A]]
-	[[Category: Lechtenberg, B C.]]	+	[[Category: Lechtenberg, B C]]
	[[Category: Hydrolase-peptide complex]]		[[Category: Hydrolase-peptide complex]]

OCA at 08:33, 18 December 2013

2013-12-18T08:33:17Z

←Older revision		Revision as of 08:33, 18 December 2013
Line 1:		Line 1:
	{{STRUCTURE_4ch2\| PDB=4ch2 \| SCENE= }}		{{STRUCTURE_4ch2\| PDB=4ch2 \| SCENE= }}
	===Low-salt crystal structure of a thrombin-GpIbalpha peptide complex===		===Low-salt crystal structure of a thrombin-GpIbalpha peptide complex===
		+	{{ABSTRACT_PUBMED_24316004}}

	==Disease==		==Disease==
Line 12:		Line 13:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:024316004</ref><references group="xtra"/><references/>
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Freund, S M.V.]]		[[Category: Freund, S M.V.]]

OCA at 13:45, 11 December 2013

2013-12-11T13:45:56Z

←Older revision		Revision as of 13:45, 11 December 2013
Line 1:		Line 1:
-	~~'''Unreleased~~ structure~~'''~~	+	{{STRUCTURE_4ch2\| PDB=4ch2 \| SCENE= }}
		+	===Low-salt crystal structure of a thrombin-GpIbalpha peptide complex===

-	The entry ~~4ch2~~ is ~~ON HOLD~~	+	==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/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref>

-	~~Authors~~: ~~Lechtenberg, B~~.C., ~~Freund~~, S.M.V., ~~Huntington~~, ~~J.A~~.	+	==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/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.

-	~~Description~~: ~~Low~~-~~salt crystal structure of a thrombin~~-~~GpIbalpha~~ peptide complex	+	==About this Structure==
		+	[[4ch2]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CH2 OCA].
		+
		+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Thrombin]]
		+	[[Category: Freund, S M.V.]]
		+	[[Category: Huntington, J A.]]
		+	[[Category: Lechtenberg, B C.]]
		+	[[Category: Hydrolase-peptide complex]]

OCA: Protected "4ch2" [edit=sysop:move=sysop]

2013-12-04T06:32:11Z

Protected "4ch2" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:32, 4 December 2013

OCA: New page: '''Unreleased structure''' The entry 4ch2 is ON HOLD Authors: Lechtenberg, B.C., Freund, S.M.V., Huntington, J.A. Description: Low-salt crystal structure of a thrombin-GpIbalpha peptid...

2013-12-04T06:32:10Z

New page: '''Unreleased structure''' The entry 4ch2 is ON HOLD Authors: Lechtenberg, B.C., Freund, S.M.V., Huntington, J.A. Description: Low-salt crystal structure of a thrombin-GpIbalpha peptid...

New page

'''Unreleased structure'''

The entry 4ch2 is ON HOLD

Authors: Lechtenberg, B.C., Freund, S.M.V., Huntington, J.A.

Description: Low-salt crystal structure of a thrombin-GpIbalpha peptide complex