4DII

X-ray structure of the complex between human alpha thrombin and thrombin binding aptamer in the presence of potassium ions

Summary for 4DII

• Entry DOI: 10.2210/pdb4dii/pdb
• Related: 4DIH
• Related PRD ID: PRD_000020
• Descriptor: Prothrombin, Thrombin binding aptamer, ZINC ION, ... (10 entities in total)
• Functional Keywords: protein-dna complex, serine protease, blood coagulation, aptamer, hydrolase-hydrolase inhibitor-dna complex, serine protease fold, dna aptamer, blood, g-quadruplex, hydrolase/hydrolase inhibitor/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 39558.81

Authors

Russo Krauss, I.,Merlino, A.,Mazzarella, L.,Sica, F. (deposition date: 2012-01-31, release date: 2012-07-18, Last modification date: 2024-10-30)

Primary citation

Russo Krauss, I.,Merlino, A.,Randazzo, A.,Novellino, E.,Mazzarella, L.,Sica, F.
High-resolution structures of two complexes between thrombin and thrombin-binding aptamer shed light on the role of cations in the aptamer inhibitory activity.
Nucleic Acids Res., 40:8119-8128, 2012

PubMed Abstract: The G-quadruplex architecture is a peculiar structure adopted by guanine-rich oligonucleotidic sequences, and, in particular, by several aptamers, including the thrombin-binding aptamer (TBA) that has the highest inhibitory activity against human α-thrombin. A crucial role in determining structure, stability and biological properties of G-quadruplexes is played by ions. In the case of TBA, K(+) ions cause an enhancement of the aptamer clotting inhibitory activity. A detailed picture of the interactions of TBA with the protein and with the ions is still lacking, despite the importance of this aptamer in biomedical field for detection and inhibition of α-thrombin. Here, we fill this gap by presenting a high-resolution crystallographic structural characterization of the thrombin-TBA complex formed in the presence of Na(+) or K(+) and a circular dichroism study of the structural stability of the aptamer both free and complexed with α-thrombin, in the presence of the two ionic species. The results indicate that the different effects exerted by Na(+) and K(+) on the inhibitory activity of TBA are related to a subtle perturbation of a few key interactions at the protein-aptamer interface. The present data, in combination with those previously obtained on the complex between α-thrombin and a modified aptamer, may allow the design of new TBA variants with a pharmacological performance enhancement.

PubMed: 22669903
DOI: 10.1093/nar/gks512

Experimental method

X-RAY DIFFRACTION (2.05 Å)