4LZ4

X-ray structure of the complex between human thrombin and the TBA deletion mutant lacking thymine 3 nucleobase

4LZ4 の概要

• エントリーDOI: 10.2210/pdb4lz4/pdb
• 関連するPDBエントリー: 3QLP 4DIH 4DII 4LZ1
• 関連するBIRD辞書のPRD_ID: PRD_000020
• 分子名称: Thrombin light chain, Thrombin heavy chain, Thrombin Binding Aptamer (TBA), ... (8 entities in total)
• 機能のキーワード: protein-dna complex, dna aptamer, g-quadruplex, tba deletion mutant, serine protease, hydrolase, blood coagulation, blood, hydrolase-dna complex, hydrolase-hydrolase inhibitor-dna complex, hydrolase/hydrolase inhibitor/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 78465.98

構造登録者

Pica, A.,Russo Krauss, I.,Merlino, A.,Sica, F. (登録日: 2013-07-31, 公開日: 2014-01-08, 最終更新日: 2024-10-30)

主引用文献

Pica, A.,Russo Krauss, I.,Merlino, A.,Nagatoishi, S.,Sugimoto, N.,Sica, F.
Dissecting the contribution of thrombin exosite I in the recognition of thrombin binding aptamer.
Febs J., 280:6581-6588, 2013

PubMed Abstract: Thrombin plays a pivotal role in the coagulation cascade; therefore, it represents a primary target in the treatment of several blood diseases. The 15-mer DNA oligonucleotide 5'-GGTTGGTGTGGTTGG-3', known as thrombin binding aptamer (TBA), is a highly potent inhibitor of the enzyme. TBA folds as an antiparallel chair-like G-quadruplex structure, with two G-tetrads surrounded by two TT loops on one side and a TGT loop on the opposite side. Previous crystallographic studies have shown that TBA binds thrombin exosite I by its TT loops, T3T4 and T12T13. In order to get a better understanding of the thrombin-TBA interaction, we have undertaken a crystallographic characterization of the complexes between thrombin and two TBA mutants, TBAΔT3 and TBAΔT12, which lack the nucleobase of T3 and T12, respectively. The structural details of the two complexes show that exosite I is actually split into two regions, which contribute differently to TBA recognition. These results provide the basis for a more rational design of new aptamers with improved therapeutic action.

PubMed: 24128303
DOI: 10.1111/febs.12561

実験手法

X-RAY DIFFRACTION (2.56 Å)