Posted by: Dan | March 20, 2007

Structural Insights into the First Enzyme

Last week’s issue of Science had an interesting article on a question central to the beginning of life on Earth. In The Structural Basis of Ribozyme-Catalyzed RNA Assembly, Robertson and Scott describe the solved structure of a class-1 ligase RNA enzyme (L1 ribozyme). This ribozyme was artificially selected to catalyze regiospecific phosphodiester bond ligation, and while it’s not the first self-replicating nucleic acid (replicase), it does catalyze the same core chemical reaction that the first replicase likely facilitated.

What Robertson and Scott found, it turns out, is that this artificially-evolved L1 ribozyme uses the same strategies as natural ribozymes and protein enzymes: transition-state stabilization and acid-base catalysis. What struck me as interesting was how the whole area of test-tube evolved ribozymes is a promising direction for back-tracking to the first replicase-catalyzed reactions. Can researchers successfully “reverse-evolve” molecules back to the first replicator?

Update: Dr. Scott was kind enough to refer us to some additional resources on the L1X6c Ligase Ribozyme Structure.


  • Robertson MP, Scott WG. The structural basis of ribozyme-catalyzed RNA assembly. Science. 2007 Mar 16;315(5818):1549-53. Pubmed
  • Joyce GF. Structural biology. A glimpse of biology’s first enzyme. Science. 2007 Mar 16;315(5818):1507-8. Pubmed
  • Bartel DP, Szostak JW. Isolation of new ribozymes from a large pool of random sequences. Science. 1993 Sep 10;261(5127):1411-8. Pubmed


  1. Funny you suggest reverse-evolution. That is my next hair-brained idea.

    Thanks again for your coverage!

    I’ve put some additional resources online.


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