4DIH: X-Ray Structure Of The Complex Between Human Alpha Thrombin And Thrombin Binding Aptamer In The Presence Of Sodium Ions

Citation:
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 alpha-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 alpha-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 alpha-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 alpha-thrombin and a modified aptamer, may allow the design of new TBA variants with a pharmacological performance enhancement.
PDB ID: 4DIHDownload
MMDB ID: 101334
PDB Deposition Date: 2012/1/31
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4DIH: trimeric; determined by author and by software (PISA)
Molecular Components in 4DIH
Label Count Molecule
Proteins (2 molecules)
1
Prothrombin(Gene symbol: F2)
Molecule annotation
1
Prothrombin(Gene symbol: F2)
Molecule annotation
Nucleotide(1 molecule)
1
Thrombin Binding Aptamer
Molecule annotation
Chemicals (9 molecules)
1
3
2
1
3
1
4
2
5
2
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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