The 1964 Experiment Where Two Wrongs Made a Right
A broken enzyme, a second mutation and an early hint of how residues talk to each other.
By The Editors/November 4, 2026/1 min read
In tryptophan synthetase, Charles Yanofsky's group found that a damaging amino acid change could be repaired by a second change somewhere else in the protein. The two positions were not neighbors in the sequence.
Protein modelers now mine that same logic statistically, across millions of sequences. In 1964 it took one enzyme, a lot of bacteria and a great deal of patience.
Sources
- Yanofsky C, Horn V, Thorpe D. Protein structure relationships revealed by mutational analysis. Science, 1964.