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.