3QLP

X-ray structure of the complex between human alpha thrombin and a modified thrombin binding aptamer (mTBA)

Summary for 3QLP

• Entry DOI: 10.2210/pdb3qlp/pdb
• Related PRD ID: PRD_000020
• Descriptor: Thrombin heavy chain, Thrombin light chain, modified thrombin binding DNA aptamer, ... (8 entities in total)
• Functional Keywords: protein-dna complex, serine protease, blood coagulation, aptamer, serine protease fold, hydrolase-hydrolase inhibitor-dna complex, hydrolase/hydrolase inhibitor/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 39357.09

Authors

Russo Krauss, I.,Merlino, A.,Mazzarella, L.,Sica, F. (deposition date: 2011-02-03, release date: 2011-10-19, Last modification date: 2024-11-06)

Primary citation

Russo Krauss, I.,Merlino, A.,Giancola, C.,Randazzo, A.,Mazzarella, L.,Sica, F.
Thrombin-aptamer recognition: a revealed ambiguity.
Nucleic Acids Res., 39:7858-7867, 2011

PubMed Abstract: Aptamers are structured oligonucleotides that recognize molecular targets and can function as direct protein inhibitors. The best-known example is the thrombin-binding aptamer, TBA, a single-stranded 15-mer DNA that inhibits the activity of thrombin, the key enzyme of coagulation cascade. TBA folds as a G-quadruplex structure, as proved by its NMR structure. The X-ray structure of the complex between TBA and human α-thrombin was solved at 2.9-Å resolution, but did not provide details of the aptamer conformation and the interactions with the protein molecule. TBA is rapidly processed by nucleases. To improve the properties of TBA, a number of modified analogs have been produced. In particular, a modified TBA containing a 5'-5' polarity inversion site, mTBA, has higher stability and higher affinity toward thrombin with respect to TBA, although it has a lower inhibitory activity. We present the crystal structure of the thrombin-mTBA complex at 2.15-Å resolution; the resulting model eventually provides a clear picture of thrombin-aptamers interaction, and also highlights the structural bases of the different properties of TBA and mTBA. Our findings open the way for a rational design of modified aptamers with improved potency as anticoagulant drugs.

PubMed: 21715374
DOI: 10.1093/nar/gkr522

Experimental method

X-RAY DIFFRACTION (2.14 Å)