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Cell. 2006 Jul 28;126(2):309-20. Epub 2006 Jul 20.

Tertiary contacts distant from the active site prime a ribozyme for catalysis.

Author information

1
Department of Molecular, Cellular and Developmental Biology, Robert L. Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.

Abstract

Minimal hammerhead ribozymes have been characterized extensively by static and time-resolved crystallography as well as numerous biochemical analyses, leading to mutually contradictory mechanistic explanations for catalysis. We present the 2.2 A resolution crystal structure of a full-length Schistosoma mansoni hammerhead ribozyme that permits us to explain the structural basis for its 1000-fold catalytic enhancement. The full-length hammerhead structure reveals how tertiary interactions occurring remotely from the active site prime this ribozyme for catalysis. G-12 and G-8 are positioned consistent with their previously suggested roles in acid-base catalysis, the nucleophile is aligned with a scissile phosphate positioned proximal to the A-9 phosphate, and previously unexplained roles of other conserved nucleotides become apparent within the context of a distinctly new fold that nonetheless accommodates the previous structural studies. These interactions permit us to explain the previously irreconcilable sets of experimental results in a unified, consistent, and unambiguous manner.

PMID:
16859740
PMCID:
PMC4447102
DOI:
10.1016/j.cell.2006.06.036
[Indexed for MEDLINE]
Free PMC Article

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