7zkn

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'''Unreleased structure'''
 
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The entry 7zkn is ON HOLD
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==X-ray structure of the complex between human alpha thrombin and a pseudo-cyclic thrombin binding aptamer (TBA-NNp/DDp) - Crystal form gamma==
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<StructureSection load='7zkn' size='340' side='right'caption='[[7zkn]], [[Resolution|resolution]] 3.03&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[7zkn]] is a 8 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=7ZKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZKN FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.03&#8491;</td></tr>
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<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=JKR:3-[5-[3-bis(oxidanyl)phosphanyloxypropoxy]naphthalen-1-yl]oxypropyl+3-(5-oxidanylnaphthalen-1-yl)oxypropyl+hydrogen+phosphate'>JKR</scene>, <scene name='pdbligand=JL0:3-oxidanylpropyl+3-[5,7,12,14-tetrakis(oxidanylidene)-13-[3-[oxidanyl-[3-[5,7,12,14-tetrakis(oxidanylidene)-13-(3-phosphonooxypropyl)-6,13-diazatetracyclo[6.6.2.0^{4,16}.0^{11,15}]hexadeca-1,3,8(16),9,11(15)-pentaen-6-yl]propoxy]phosphoryl]oxypropyl]-6,13-diazatetracyclo[6.6.2.0^{4,16}.0^{11,15}]hexadeca-1(15),2,4(16),8,10-pentaen-6-yl]propyl+hydrogen+phosphate'>JL0</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zkn OCA], [https://pdbe.org/7zkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zkn RCSB], [https://www.ebi.ac.uk/pdbsum/7zkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zkn ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Despite their unquestionable properties, oligonucleotide aptamers display some drawbacks that continue to hinder their applications. Several strategies have been undertaken to overcome these weaknesses, using thrombin binding aptamers as proof-of-concept. In particular, the functionalization of a thrombin exosite I binding aptamer (TBA) with aromatic moieties, e.g., naphthalene dimides (N) and dialkoxynaphthalenes (D), attached at the 5' and 3' ends, respectively, proved to be highly promising. To obtain a molecular view of the effects of these modifications on aptamers, we performed a crystallographic analysis of one of these engineered oligonucleotides (TBA-NNp/DDp) in complex with thrombin. Surprisingly, three of the four examined crystallographic structures are ternary complexes in which thrombin binds a TBA-NNp/DDp molecule at exosite II as well as at exosite I, highlighting the ability of this aptamer, differently from unmodified TBA, to also recognize a localized region of exosite II. This novel ability is strictly related to the solvophobic behavior of the terminal modifications. Studies were also performed in solution to examine the properties of TBA-NNp/DDp in a crystal-free environment. The present results throw new light on the importance of appendages inducing a pseudo-cyclic charge-transfer structure in nucleic acid-based ligands to improve the interactions with proteins, thus considerably widening their potentialities.
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Authors: Troisi, R., Sica, F.
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A terminal functionalization strategy reveals unusual binding abilities of anti-thrombin anticoagulant aptamers.,Troisi R, Riccardi C, Perez de Carvasal K, Smietana M, Morvan F, Del Vecchio P, Montesarchio D, Sica F Mol Ther Nucleic Acids. 2022 Nov 15;30:585-594. doi: 10.1016/j.omtn.2022.11.007. , eCollection 2022 Dec 13. PMID:36457701<ref>PMID:36457701</ref>
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Description: X-ray structure of the complex between human alpha thrombin and a pseudo-cyclic thrombin binding aptamer (TBA-NNp/DDp) -Crystal form gamma
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Troisi, R]]
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<div class="pdbe-citations 7zkn" style="background-color:#fffaf0;"></div>
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[[Category: Sica, F]]
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==See Also==
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*[[Thrombin 3D Structures|Thrombin 3D Structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Synthetic construct]]
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[[Category: Sica F]]
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[[Category: Troisi R]]

Current revision

X-ray structure of the complex between human alpha thrombin and a pseudo-cyclic thrombin binding aptamer (TBA-NNp/DDp) - Crystal form gamma

PDB ID 7zkn

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