6gn7 - Revision history

OCA at 07:03, 27 March 2019

2019-03-27T07:03:09Z

←Older revision		Revision as of 07:03, 27 March 2019
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	==X-ray structure of the complex between human alpha thrombin and NU172, a duplex/quadruplex 26-mer DNA aptamer, in the presence of sodium ions.==		==X-ray structure of the complex between human alpha thrombin and NU172, a duplex/quadruplex 26-mer DNA aptamer, in the presence of sodium ions.==
-	<StructureSection load='6gn7' size='340' side='right' caption='[[6gn7]], [[Resolution\|resolution]] 2.80Å' scene=''>	+	<StructureSection load='6gn7' size='340' side='right'caption='[[6gn7]], [[Resolution\|resolution]] 2.80Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6gn7]] 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=6GN7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GN7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6gn7]] 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=6GN7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GN7 FirstGlance]. <br>
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	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Krauss, I Russo]]		[[Category: Krauss, I Russo]]

OCA at 12:48, 7 November 2018

2018-11-07T12:48:42Z

←Older revision		Revision as of 12:48, 7 November 2018
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	== 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/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 ==
		+	Despite aptamers are very promising alternative to antibodies, very few of them are under clinical trials or are used as drugs. Among them, NU172 is currently in Phase II as anticoagulant in heart disease treatments. It inhibits thrombin activity much more effectively than TBA, the best-known thrombin binding aptamer. The crystal structure of thrombin-NU172 complex reveals a bimodular duplex/quadruplex architecture for the aptamer, which binds thrombin exosite I through a highly complementary surface involving all three loops of the G-quadruplex module. Although the duplex domain does not interact directly with thrombin, the features of the duplex/quadruplex junction and the solution data on two newly designed NU172 mutants indicate that the duplex moiety is important for the optimization of the protein-ligand interaction and for the inhibition of the enzyme activity. Our work discloses the structural features determining the inhibition of thrombin by NU172 and put the basis for the design of mutants with improved properties.
		+
		+	Several structural motifs cooperate in determining the highly effective anti-thrombin activity of NU172 aptamer.,Troisi R, Napolitano V, Spiridonova V, Russo Krauss I, Sica F Nucleic Acids Res. 2018 Oct 24. pii: 5144158. doi: 10.1093/nar/gky990. PMID:30357392<ref>PMID:30357392</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6gn7" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 08:08, 17 October 2018

2018-10-17T08:08:53Z

←Older revision		Revision as of 08:08, 17 October 2018
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-	'''Unreleased structure'''

-	~~The entry 6gn7 is ON HOLD until Paper Publication~~	+	==X-ray structure of the complex between human alpha thrombin and NU172, a duplex/quadruplex 26-mer DNA aptamer, in the presence of sodium ions.==
-		+	<StructureSection load='6gn7' size='340' side='right' caption='[[6gn7]], [[Resolution\|resolution]] 2.80Å' scene=''>
-	~~Authors: Troisi, R., Russo Krauss, I., Sica, F.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6gn7]] 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=6GN7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GN7 FirstGlance]. <br>
-	~~Description:~~ X-ray structure of the complex between human alpha thrombin and NU172, a duplex/quadruplex 26-mer DNA aptamer, in the presence of sodium ions.	+	</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=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SIA:O-SIALIC+ACID'>SIA</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[6evv\|6evv]]</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=6gn7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gn7 OCA], [http://pdbe.org/6gn7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gn7 RCSB], [http://www.ebi.ac.uk/pdbsum/6gn7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gn7 ProSAT]</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Thrombin]]
		+	[[Category: Krauss, I Russo]]
	[[Category: Sica, F]]		[[Category: Sica, F]]
	[[Category: Troisi, R]]		[[Category: Troisi, R]]
-	[[Category: ~~Russo Krauss, I~~]]	+	[[Category: Aptamer]]
		+	[[Category: Duplex/quadruplex]]
		+	[[Category: G-quadruplex]]
		+	[[Category: Hydrolase]]
		+	[[Category: Thrombin-dna]]

OCA: Protected "6gn7" [edit=sysop:move=sysop]

2018-06-06T04:31:01Z

Protected "6gn7" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:31, 6 June 2018

OCA: New page: '''Unreleased structure''' The entry 6gn7 is ON HOLD until Paper Publication Authors: Troisi, R., Russo Krauss, I., Sica, F. Description: X-ray structure of the complex between human a...

2018-06-06T04:31:00Z

New page: '''Unreleased structure''' The entry 6gn7 is ON HOLD until Paper Publication Authors: Troisi, R., Russo Krauss, I., Sica, F. Description: X-ray structure of the complex between human a...

New page

'''Unreleased structure'''

The entry 6gn7 is ON HOLD until Paper Publication

Authors: Troisi, R., Russo Krauss, I., Sica, F.

Description: X-ray structure of the complex between human alpha thrombin and NU172, a duplex/quadruplex 26-mer DNA aptamer, in the presence of sodium ions.
[[Category: Unreleased Structures]]
[[Category: Sica, F]]
[[Category: Troisi, R]]
[[Category: Russo Krauss, I]]