Volume 1, Issue 5
Berkeley's Scientific Legacy
1958: Daniel Koshland and shape-shifting proteins
Among Daniel Koshland's honors are the National Medal of Science, the Edgar Fahs Smith and Pauling Awards of the American Chemical Society, the Rosenstiel Award of Brandeis University, the Waterford Prize, and the Merck Award of the American Society of Biochemistry and Molecular Biology.
Inside our bodies, an intricate dance of mechanical motion is taking place. At the cellular level, the proteins that are the building blocks of life are shifting their shape as they interact, flexing as they bind in a biophysical ballet.
In the 1960s, UC Berkeley biochemist Daniel E. Koshland formulated new theories that changed science's fundamental understanding of this complex choreography. His discoveries helped lay the groundwork for decades of research on the relationship between protein structure and function and the correlation of protein chemistry to various diseases.
Koshland, who obtained his BS in chemistry from Berkeley in 1941, is best known for his "induced fit theory," an explanation he first proposed in 1958 of how enzymes catalyze the chemical reactions of life, converting one substance into another. At the time, scientists supported a theory first laid out in 1894 that enzymes are like locks with the compounds they affect acting as keys. When one fits into the other, catalysis occurs.
Koshland argued that the rigid key-lock theory didn't explain the specificity and regulation demonstrated by many reactions. In many cases, he believed, the enzyme is flexible and the compound binds to it like a hand inside a glove. If the hand (the substrate) is too big to fit or too little to fill the glove (the enzyme), the reaction won't occur.
It wasn't until the 1970s that the induced fit theory was verified using X-ray crystallography, a technique to visualize the location of atoms in a protein. Meanwhile, Koshland's further research led to insights into hormone interactions and the mechanisms by which biological processes are regulated.
In 1998, Koshland was awarded the prestigious Albert Lasker Award for Special Achievement in Medical Science. He has published more than 400 scientific papers and was the editor of Science magazine from 1985-1995. During more than three decades as a Berkeley researcher and professor, Koshland was instrumental in focusing and growing Berkeley's biological sciences.
Still a Professor of the Graduate School in the Department of Molecular and Cell Biology, Koshland, 85, continues his research on proteins. Currently, he's applying genetic engineering and protein chemistry to design therapies for Alzheimer's Disease and exploring how enzymes might be modified for use in environmental clean-up.