Back to the future: Ribonuclease A

Garland R. Marshall, Jiawen A. Feng, Daniel J. Kuster

Research output: Contribution to journalReview articlepeer-review

78 Scopus citations


Pancreatic-ribonuclease A (EC, RNase) is, perhaps, the best-studied enzyme of the 20th century. It was isolated by René Dubos, crystallized by Moses Kunitz, sequenced by Stanford Moore and William Stein, and synthesized in the laboratory of Bruce Merrifield, all at the Rockefeller Institute/University, It has proven to be an excellent model system for many different types of experiments, both as an enzyme and as a well-characterized protein for biophysical studies. Of major significance was the demonstration by Chris Arfinsen at NIH that the primary sequence of RNase encoded the three-dimensional structure of the enzyme. Many other prominent protein chemists/ enzymologists have utilized RNase as a dominant theme in their research. In this review, the history of RNase and its offspring, RNase S (S-protein/S-peptide), will be considered, especially the work in the Merrifield group, as a preface to preliminary data and proposed experiments addressing topics of current interest. These include entropy-enthalpy compensation, entropy of ligand binding, the impact of protein modification on thermal stability, and the role of protein dynamics in enzyme action. In containing to use RNase as a prototypical enzyme, we stand on the shoulders of the giants of protein chemistry to survey the future.

Original languageEnglish
Pages (from-to)259-277
Number of pages19
JournalBiopolymers - Peptide Science Section
Issue number3
StatePublished - 2008


  • Chimeric enzyme
  • Protein dynamics
  • Ribonuclease A
  • S-peptide
  • S-protein


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