OCA at 13:43, 24 January 2024

OCA — Wed, 24 Jan 2024 13:43:58 GMT

←Older revision		Revision as of 13:43, 24 January 2024
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-	====	+	==X-ray structure of the complex between human alpha thrombin and a thrombin binding aptamer variant (TBA-3G), which contains 1-beta-D-glucopyranosyl residue in the side chain of Thy3 at N3.==
-	<StructureSection load='6z8w' size='340' side='right'caption='[[6z8w]]' scene=''>	+	<StructureSection load='6z8w' size='340' side='right'caption='[[6z8w]], [[Resolution\|resolution]] 1.73Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6z8w]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z8W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z8W FirstGlance]. <br>
-	</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=6z8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z8w OCA], [https://pdbe.org/6z8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z8w RCSB], [https://www.ebi.ac.uk/pdbsum/6z8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z8w ProSAT]</span></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]] 1.73Å</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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=QCK:(4-methyltriazole)-Thymidine-5-monophosphate'>QCK</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=6z8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z8w OCA], [https://pdbe.org/6z8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z8w RCSB], [https://www.ebi.ac.uk/pdbsum/6z8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z8w ProSAT]</span></td></tr>
	</table>		</table>
		+	== 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>
		+	== 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Post-SELEX modification of DNA aptamers is an established strategy to improve their affinity or inhibitory characteristics. In this study, we examined the possibility of increasing the recognition interface between the thrombin-binding aptamer HD1 (TBA) and thrombin by adding a chemically modified side chain to selected nucleotide residues. A panel of 22 TBA variants with N3-modified residues T3 and T12 was prepared by a two-step modification procedure. Aptamers were characterized by a combination of biophysical and biochemical methods. We identified mutants with enhanced affinity and improved anticoagulant activity. The crystal structures of thrombin complexes with three selected modified variants revealed that the modified pyrimidine base invariably allocates in proximity to thrombin residues Tyr76 and Ile82 due to the directing role of the unmodified TT loop. The modifications induced an increase in the contact areas between thrombin and the modified TBAs. Comparative analysis of the structural, biochemical, and biophysical data suggests that the non-equivalent binding modes of the mutants with thrombin in the T3- and T12-modified series account for the observed systematic differences in their affinity characteristics. In this study, we show that extending the recognition surface between the protein and modified aptamers is a promising approach that may improve characteristics of aptamer ligands.
		+
		+	Expanding the recognition interface of the thrombin-binding aptamer HD1 through modification of residues T3 and T12.,Smirnov I, Kolganova N, Troisi R, Sica F, Timofeev E Mol Ther Nucleic Acids. 2021 Jan 16;23:863-871. doi: 10.1016/j.omtn.2021.01.004. , eCollection 2021 Mar 5. PMID:33614235<ref>PMID:33614235</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6z8w" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Thrombin 3D Structures\|Thrombin 3D Structures]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Z-disk~~]]	+	[[Category: Synthetic construct]]
		+	[[Category: Sica F]]
		+	[[Category: Timofeev EN]]
		+	[[Category: Troisi R]]

OCA at 07:55, 27 January 2021

OCA — Wed, 27 Jan 2021 07:55:47 GMT

←Older revision		Revision as of 07:55, 27 January 2021
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6z8w ~~is ON HOLD until Paper Publication~~	+	====
-		+	<StructureSection load='6z8w' size='340' side='right'caption='[[6z8w]]' scene=''>
-	~~Authors~~: ~~Troisi, R~~.~~, Timofeev, E~~.N.~~, Sica, F.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
-	~~Description: X~~-~~ray structure of the complex between human alpha thrombin and~~ a ~~thrombin binding aptamer variant (TBA-3G), which contains 1-beta-D-glucopyranosyl residue in~~ the ~~side chain of Thy3 at N3~~.	+	</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=6z8w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z8w OCA], [https://pdbe.org/6z8w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z8w RCSB], [https://www.ebi.ac.uk/pdbsum/6z8w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z8w ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Timofeev~~, E.N]]	+	__TOC__
-	[[Category: ~~Troisi, R~~]]	+	</StructureSection>
-	[[Category: ~~Sica, F~~]]	+	[[Category: Large Structures]]
		+	[[Category: Z-disk]]

OCA at 08:09, 12 August 2020

OCA — Wed, 12 Aug 2020 08:09:50 GMT

←Older revision		Revision as of 08:09, 12 August 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6z8w is ON HOLD	+	The entry 6z8w is ON HOLD until Paper Publication

	Authors: Troisi, R., Timofeev, E.N., Sica, F.		Authors: Troisi, R., Timofeev, E.N., Sica, F.

OCA: Protected "6z8w" [edit=sysop:move=sysop]

OCA — Wed, 10 Jun 2020 05:11:18 GMT

Protected "6z8w" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:11, 10 June 2020

OCA: New page: '''Unreleased structure''' The entry 6z8w is ON HOLD Authors: Troisi, R., Timofeev, E.N., Sica, F. Description: X-ray structure of the complex between human alpha thrombin and a thromb...

OCA — Wed, 10 Jun 2020 05:11:16 GMT

New page: '''Unreleased structure''' The entry 6z8w is ON HOLD Authors: Troisi, R., Timofeev, E.N., Sica, F. Description: X-ray structure of the complex between human alpha thrombin and a thromb...

New page

'''Unreleased structure'''

The entry 6z8w is ON HOLD

Authors: Troisi, R., Timofeev, E.N., Sica, F.

Description: X-ray structure of the complex between human alpha thrombin and a thrombin binding aptamer variant (TBA-3G), which contains 1-beta-D-glucopyranosyl residue in the side chain of Thy3 at N3.
[[Category: Unreleased Structures]]
[[Category: Timofeev, E.N]]
[[Category: Troisi, R]]
[[Category: Sica, F]]

6z8w - Revision history

OCA at 13:43, 24 January 2024

OCA at 07:55, 27 January 2021

OCA at 08:09, 12 August 2020

OCA: Protected "6z8w" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 6z8w is ON HOLD Authors: Troisi, R., Timofeev, E.N., Sica, F. Description: X-ray structure of the complex between human alpha thrombin and a thromb...