Ribonuclease A: from Model System to Cancer Chemotherapeutic

Ribonuclease A has been the most studied enzyme of the twentieth century. Work on ribonuclease A has endowed enzymology, as well as protein science, with many paradigms. This work continues to provide a framework for understanding protein structure – function relationships in atomic detail. In addition, knowledge gained by basic research is enabling the rapid deployment of ribonuclease A homologs and variants as chemotherapeutic agents for the treatment of cancer and other human diseases. For the last fifty years, chemists and biochemists have been investigating the origins of the extraordinary effectiveness of enzymes as catalysts. The aims have been to identify the reaction intermediates, to measure the rates of their interconversion, and to determine the precise role of amino acid residues in the process. A variety of enzymes have contributed to this understanding. One of these enzymes is bovine pancreatic ribonuclease A (RNase A; EC 3.1.27.5). RNase A has been the object of landmark work in enzymology, as well as on the folding, stability, and chemistry of proteins, and on molecular evolution [1,2]. The seminal contributions of RNase A to chemistry was recognized by the awarding of Nobel Prizes to Anfinsen, Stein, and Moore in 1972, and to Merrifield in 1984. Each of these laureates chose RNase A as his model system.