3-DIMENSIONAL STRUCTURE OF A HAMMERHEAD RIBOZYME

The hammerhead ribozyme is a small catalytic RNA motif made up of thre e base-paired stems and a core of highly conserved, non-complementary nucleotides essential for catalysis. The X-ray crystallographic struct ure of a hammerhead RNA-RNA ribozyme-inhibitor complex at 2.6 Angstrom resolution reveals that the base-paired stems are A-form helices and that the core has two structural domains. The first domain is formed b y the sequence 5'-CUGA following stem I and is a sharp turn identical to the uridine turn of transfer RNA, whereas the second is a non-Watso n-Crick three-base-pair duplex with a divalent-ion binding site. The p hosphodiester backbone of the DNA inhibitor strand is splayed out at t he phosphate 5' to the cleavage site. The structure indicates that the ribozyme may destabilize a substrate strand in order to facilitate tw isting of the substrate to allow cleavage of the scissile bond.