7zko: Difference between revisions
New page: '''Unreleased structure''' The entry 7zko is ON HOLD Authors: Troisi, R., Sica, F. Description: X-ray structure of the complex between human alpha thrombin and a pseudo-cyclic thrombin... |
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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 delta== | |||
<StructureSection load='7zko' size='340' side='right'caption='[[7zko]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7zko]] is a 4 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=7ZKO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZKO FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</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=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=NA:SODIUM+ION'>NA</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=7zko FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zko OCA], [https://pdbe.org/7zko PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zko RCSB], [https://www.ebi.ac.uk/pdbsum/7zko PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zko ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7zko" style="background-color:#fffaf0;"></div> | ||
[[Category: Sica | |||
==See Also== | |||
*[[Thrombin 3D Structures|Thrombin 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Synthetic construct]] | |||
[[Category: Sica F]] | |||
[[Category: Troisi R]] | |||
Latest revision as of 12:24, 17 October 2024
X-ray structure of the complex between human alpha thrombin and a pseudo-cyclic thrombin binding aptamer (TBA-NNp/DDp) - Crystal form deltaX-ray structure of the complex between human alpha thrombin and a pseudo-cyclic thrombin binding aptamer (TBA-NNp/DDp) - Crystal form delta
Structural highlights
Publication Abstract from PubMedDespite 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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