429D

Crystal structure of a lead-dependent ribozyme revealing metal binding sites relevant to catalysis.

(1999) Nat Struct Biol 6: 261-268

• PubMed: 10074945 Search on PubMed
• DOI: https://doi.org/10.1038/6700
• Primary Citation of Related Structures:  
  429D


• PubMed Abstract: 
  

  The leadzyme is a small RNA motif that catalyzes a site-specific, Pb2+-dependent cleavage reaction. As such, it is an example of a metal-dependent RNA enzyme. Here we describe the X-ray crystallographic structure of the leadzyme, which reveals two independent molecules per asymmetric unit. Both molecules feature an internal loop in which a bulged purine base stack twists away from the helical stem. This kinks the backbone, rendering the phosphodiester bond susceptible to cleavage. The independent molecules have different conformations: one leadzyme copy coordinates Mg2+, whereas the other binds only Ba2+ or Pb2+. In the active site of the latter molecule, a single Ba2+ ion coordinates the 2'-OH nucleophile, and appears to mimic the binding of catalytic lead. These observations allow a bond cleavage reaction to be modeled, which reveals the minimal structural features necessary for catalysis by this small ribozyme.

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Organizational Affiliation: 

Department of Structural Biology, Stanford University School of Medicine, California 94305-5126, USA. Wedekind@ribose.stanford.edu