Biochemist Christian Boehmer Anfinsen is known for establishing that the structure of an enzyme is intimately related to its function. This discovery was a major contribution to the scientific understanding of the nature of enzymes. For this achievement, Anfinsen shared the 1972 Nobel Prize for Chemistry with the research team of Stanford Moore and William Howard Stein.
Anfinsen was born on March 26, 1916, in Monessen, Pennsylvania, a town located just outside of Pittsburgh. He was the child of Christian Anfinsen, an engineer and emigrant from Norway, and Sophie Rasmussen, who was also of Norwegian heritage. Anfinsen earned his B.A. from Swarthmore College in 1937. Subsequently, he attended the University of Pennsylvania, earning an M.S. in organic chemistry in 1939. After earning his master's degree, Anfinsen received a fellowship from the American Scandinavian Foundation to spend a year at the Carlsberg Laboratory in Copenhagen, Denmark. Upon his return in 1940, he entered Harvard University's Ph.D. program in biochemistry. His doctoral dissertation involved work with enzymes; he described various methodologies for discerning the enzymes present in the retina of the eye, and he earned his Ph.D in 1943.
After receiving his Ph.D., Anfinsen began teaching at Harvard Medical School, in the department of biological chemistry. From 1944 to 1946 he worked in the United States Office of Scientific Research and Development. He then worked in the biochemical division of the Medical Nobel Institute in Sweden under Hugo Theorell, as an American Cancer Society senior fellow, from 1947 to 1948. Harvard University promoted him to associate professor upon his return, but in 1950 he accepted a position as head of the National Institutes of Health's (NIH) National Heart Institute Laboratory of Cellular Physiology. He served in this position until 1962. Anfinsen returned to teaching at Harvard Medical School in 1962, but he returned to NIH a year later. This time he was named director of the Laboratory of Chemical Biology at the National Institute of Arthritis, Metabolism, and Digestive Diseases. He held this position until 1981; he spent a year at the Weizmann Institute of science and then in 1982 accepted an appointment as professor of biology at Johns Hopkins University, where he remained until his death. A former editor of Advances in Protein Chemistry, he was also on the editorial boards of the Journal of Biological Chemistry, Biopolymers, and the Proceedings of the National Academy of Sciences.
Anfinsen began his research concerning the structure and function of enzymes in the mid-1940s. Enzymes are a type of protein; specifically, they are what drives the many chemical reactions in the human body. All proteins are made up of smaller components called peptide chains, which are amino acids linked together. Amino acids are, in turn, a certain class of organic compounds. The enzymes take on a globular, three-dimensional, form as the amino acid chain folds over. The unfolded chain form of an enzyme is called the primary structure. Once the chain folds over, it is said to be in the tertiary structure. From one set of amino acids for one particular enzyme there are 100 different possible ways in which these amino acids can link together. (Only certain amino acids can "fit" next to other amino acids.) However, only one configuration will result in an active enzyme. In general, Anfinsen's research concerned finding out how a particular set of amino acids knows to configure in a way that results in the active form of the enzyme.
Anfinsen chose to study the enzyme ribonuclease (RNase), which contains 124 amino acids and is responsible for breaking down the ribonucleic acid (RNA) found in food. This reaction enables the body to recycle the resultant smaller pieces. He felt that by determining how a particular enzyme assumes its particular active configuration, the structure and function of enzymes could be better understood. He reasoned that he could determine how an enzyme protein is built and when the enzyme becomes functional by observing it adding one amino acid at a time. He utilized techniques developed by Cambridge University's Frederick Sanger to conduct this research. Another research team headed by Stanford Moore and William Howard Stein was working simultaneously on the same enzyme as Anfinsen, ribonuclease; in 1960, using ribonuclease, Moore and Stein were the first to determine the exact amino acid sequence of an enzyme. However, Anfinsen remained more concerned with how the enzyme forms into its active configuration.
Anfinsen eventually changed his methodology of research during an opportunity to study abroad. While at the NIH, Anfinsen took yet another leave of absence when a Rockefeller Public Service Award allowed him to spend 1954 to 1955 at the Carlsberg Laboratory studying under the physical chemist Kai Linderstrøm-Lang. Anfinsen had been studying ribonuclease by building it up; Linderstrøm-Lang convinced him to start with the whole molecule and study it by stripping it down piece by piece. Anfinsen began with the whole ribonuclease molecule and then successively broke the various bonds of the molecule. The process is called denaturing the protein or, in other words, causing it to lose its functional capacity. By breaking certain key bonds, other bonds formed between the amino acids resulting in a random, inactive form of ribonuclease. By 1962, Anfinsen had confirmed that when this inactive form is placed into an environment that mimics the environment in which ribonuclease normally appears in the body, that inactive form would slowly revert to the active configuration on its own and thus regain its enzymatic activity. This discovery revealed the important fact that all the information for the assembly of the three-dimensional, active enzyme form was within the protein's own sequence of amino acids.
Receives Nobel Prize for Enzyme Research
For uncovering the connection between the primary and tertiary structure of enzymes, Anfinsen received half of the 1972 Nobel Prize for Chemistry. Moore and Stein and were awarded the other half. In addition to his numerous journal articles on protein structure, enzyme function, and related matters, in 1959, Anfinsen published a book entitled The Molecular Basis of Evolution. After receiving the Nobel Prize, Anfinsen began focusing his research on the protein interferon, known for its key role as part of the body's immunity against both viruses and cancer. He succeeded in isolating and characterizing this important human protein.
Anfinsen's honors in addition to the Nobel Prize include The Rockefeller Foundation Public Service Award, a Guggenheim Fellowship, as well as honorary degrees from Georgetown University and New York Medical College and five other universities. Anfinsen was a member of the National Academy of Sciences, the American Society of Biological Chemists, and the Royal Danish Academy. As an opponent of biological weapons, he belonged to the Committee for Responsible Genetics. He married Florence Bernice Kenenger in 1941, and they had three children. Anfinsen and Kenenger divorced in 1978. In 1979, Anfinsen married Libby Esther Schulman Ely. He died on 14 May, 1995, at Northwest Hospital Center in Randallstown, MD.
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