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Three-dimensional structure of a hammerhead ribozyme

Abstract

The hammerhead ribozyme is a small catalytic RNA motif made up of three base-paired stems and a core of highly conserved, non-complementary nucleotides essential for catalysis. The X-ray crystallographic structure of a hammerhead RNA–DNA ribozyme-inhibitor complex at 2.6 Å resolution reveals that the base-paired stems are A-form helices and that the core has two structural domains. The first domain is formed by 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-Watson–Crick three-base-pair duplex with a divalent-ion binding site. The phosphodiester back-bone of the DNA inhibitor strand is splayed out at the phosphate 5′ to the cleavage site. The structure indicates that the ribozyme may destabilize a substrate strand in order to facilitate twisting of the substrate to allow cleavage of the scissile bond.

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Pley, H., Flaherty, K. & McKay, D. Three-dimensional structure of a hammerhead ribozyme. Nature 372, 68–74 (1994). https://doi.org/10.1038/372068a0

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