title: Back to the future: ribonuclease A.
abstract: Pancreatic ribonuclease A (EC 3.1.27.5, 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 Anfinsen 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 continuing to use RNase as a prototypical enzyme, we stand on the shoulders of the giants of protein chemistry to survey the future.
authors.affiliation: Center for Computational Biology, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA. garland@pcg.wustl.edu
authors.forename: Garland R
authors.initials: GR
authors.lastname: Marshall
authors.forename: Jiawen A
authors.initials: JA
authors.lastname: Feng
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kuster
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003198:Computer Simulation; D019277:Entropy; D005544:Forecasting; D049673:History, 20th Century; D008958:Models, Molecular; D011487:Protein Conformation; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D012259:Ribonuclease, Pancreatic / Q000737:chemistry* / Q000266:history* / Q000302:isolation & purification
chemical_list: D012259:Ribonuclease, Pancreatic