Crystallization and Preliminary X-Ray Crystallographic Analysis of the Complex of Human Alpha Thrombin With A Modified Thrombin Binding Aptamer

The thrombin-binding aptamer (TBA) is a consensus DNA 15-mer that binds specifically to human [alpha]-thrombin at nanomolar concentrations and inhibits its procoagulant functions. Recently, a modified TBA (mTBA) containing a 5'-5' inversion-of-polarity site has been shown to be more stable and to possess a higher thrombin affinity than its unmodified counterpart. The structure of the thrombin-TBA complex has previously been determined at low resolution, but did not provide a detailed picture of the aptamer conformation or of the protein-DNA assembly, while that of the complex with mTBA is unknown. Crystallographic analysis of the thrombin-mTBA complex has been attempted. The crystals diffracted to 2.15 Å resolution and belonged to space group I222.