A PREORGANIZED ACTIVE-SITE IN THE CRYSTAL-STRUCTURE OF THE TETRAHYMENA RIBOZYME

Group I introns possess a single active site that catalyzes the two se quential reactions of self-splicing. An RNA comprising the two domains of the Tetrahymena thermophila group I intron catalytic core retains activity, and the 5.0 angstrom crystal structure of this 247-nucleotid e ribozyme is now described. Close packing of the two domains forms a shallow cleft capable of binding the short helix that contains the 5' splice site. The helix that provides the binding site for the guanosin e substrate deviates significantly from A-form geometry, providing a t ight binding pocket. The binding pockets for both the 5' splice site h elix and guanosine are formed and oriented in the absence of these sub strates. Thus, this large ribozyme is largely preorganized for catalys is, much Like a globular protein enzyme.