By Ribosome PossessedI'll play it, and tell you what it is later.—Miles Davis
The Tryptophan Synthase α2β2 Complex: A Model for Substrate Channeling, Allosteric Communication, and Pyridoxal Phosphate CatalysisI reflect on my research on pyridoxal phosphate (PLP) enzymes over fifty-five years and on how I combined research with marriage and family. My Ph.D. research with Esmond E. Snell established one aspect of PLP enzyme mechanism. My postdoctoral work first with Hans L. Kornberg and then with Alton Meister characterized the structure and function of another PLP enzyme, l-aspartate β-decarboxylase. My independent research at the National Institutes of Health (NIH) since 1966 has focused on the bacterial tryptophan synthase α2β2 complex.
How Enzymes Handle the Energy Derived from the Cleavage of High-energy Phosphate CompoundsI was accepted at the Federal University of Rio de Janeiro Medical School when I was seventeen years old. At that time, I was absolutely sure I was going to be a surgeon. One year later, I received an offer for a fellowship to work in a research laboratory. This originally had not been part of my future professional plan, but I was desperately in need of a source of income, so I joined the research laboratory at the age of eighteen. During the medical school course in Rio de Janeiro, I lived the hormonal tempest typical of youth, and my certainties were shaken badly.
Five Decades with Glutathione and the GSTomeUncle Folke inspired me to become a biochemist by demonstrating electrophoresis experiments on butterfly hemolymph in his kitchen. Glutathione became the subject for my undergraduate project in 1964 and has remained a focal point in my research owing to its multifarious roles in the cell. Since the 1960s, the multiple forms of glutathione transferase (GST), the GSTome, were isolated and characterized, some of which were discovered in our laboratory. Products of oxidative processes were found to be natural GST substrates.
Wandering through the LaboratoryI got my start in biochemistry because of the Vietnam War. As I was finishing my medical residency at Massachusetts General Hospital in 1963, I had two choices going forward: either I could go to Vietnam as a physician, or I could become a research associate in the United States Public Health Service at the National Institutes of Health (NIH). The choice was easy. I considered several laboratories at NIH. I could choose freely because research associates came with their own salaries, so they had no effect on the budget of the laboratory in which they worked.
Benefits from Unearthing “a Biochemical Rosetta Stone”In reflecting about incidents, accomplishments, and disappointments that occurred during my career, many of them seem almost apocryphal. I acquired an interest in lipids in my third year at Harvard Medical School when I was caring for a young woman with a severe heart problem at the then-Boston City Hospital. World War II was in full swing, and medical students were intimately involved in the care and treatment of patients. She had two young children and a devoted husband, who was truly grateful for any help I could provide.
Catalysis at the Intersection of Biology, Chemistry, and MedicineI have been exceptionally fortunate to hold, as my only professional jobs, faculty positions at two outstanding research-intensive universities, the Massachusetts Institute of Technology (MIT) and Harvard University, for almost four decades. This has been an opportunity to work with many of the world's best colleagues and predoctoral and postdoctoral students and to get an unparalleled and continuous education in the exciting scientific currents of this period. While at MIT, I had appointments in both the departments of chemistry and biology as my own personal bridging-biochemistry experience.
A Lifetime of Playing with EnzymesI was born and raised in a small town in southeastern Kansas called Hepler. I attended grammar school and high school in Hepler, and the student body of the high school was approximately 100. The United States entered World War II during my sophomore year, and accelerated programs allowed me to skip my senior year, so I enrolled in college in the summer of 1943. I was 16 years old. I also volunteered for the United States Air Force cadet training program when I was 16. I enrolled in Valparaiso University in Indiana in the fall of 1943; however, my first year at Valpo was not terribly productive.