7ZKM

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

7ZKM の概要

• エントリーDOI: 10.2210/pdb7zkm/pdb
• 関連するPDBエントリー: 7ZKL 7ZKN 7ZKO
• 分子名称: Thrombin light chain, Thrombin heavy chain, TBA-NNp/DDp, ... (10 entities in total)
• 機能のキーワード: thrombin, aptamer, complex, inhibitor, coagulation, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 47672.94

構造登録者

Troisi, R.,Sica, F. (登録日: 2022-04-13, 公開日: 2022-11-30, 最終更新日: 2024-11-13)

主引用文献

Troisi, R.,Riccardi, C.,Perez de Carvasal, K.,Smietana, M.,Morvan, F.,Del Vecchio, P.,Montesarchio, D.,Sica, F.
A terminal functionalization strategy reveals unusual binding abilities of anti-thrombin anticoagulant aptamers.
Mol Ther Nucleic Acids, 30:585-594, 2022

PubMed Abstract: 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 -cyclic charge-transfer structure in nucleic acid-based ligands to improve the interactions with proteins, thus considerably widening their potentialities.

PubMed: 36457701
DOI: 10.1016/j.omtn.2022.11.007

実験手法

X-RAY DIFFRACTION (2 Å)