• DOI:10.1002/ANIE.199423751
• Corpus ID: 10984112

The Key–Lock Theory and the Induced Fit Theory

@article{Koshland1995TheKT,
  title={The Key–Lock Theory and the Induced Fit Theory},
  author={Daniel E. Koshland},
  journal={Angewandte Chemie},
  year={1995},
  volume={33},
  pages={2375-2378}
}

• D. Koshland
• Published 3 January 1995
• Biology
• Angewandte Chemie

It is a great pleasure for me to contribute to this symposium honoring the great scientist Emil Fischer. My graduate thesis required me to synthesize [1-14C]glucose, which introduced me to the famous Fischer-Kiliani synthesis of glucose and mannose from arabinose and HCN. [1] I was also particularly intrigued with his classic key-lock (or template) theory of enzyme specificity,[2, 3 ] which like all great theories seemed so obvious once one understood it. This symposium in his honor allows me to pay tribute to Fischer’s great contributions to biochemistry varying from natural products chemistry to the key-lock theory, to review some of the history and significance of our induced fit theory, to illustrate the ramifications of those theories in our present era of protein-ligand interactions, and to discuss recent work in our laboratory which is helping to clarify conformational changes and their function. These theories have assumed again a central role in modern health research where the need for drug design requires taking into account the complementarity of fit of Fischer’s principle and the flexibility and regulatory implications of the induced fit theory. The induced fit theory is no more a refutation of Fischer’s key-lock principle than the Heisenberg atom was of the Bohr atom or the modern DNA sequences are of the one gene-one enzyme hypothesis. A new theory must explain all the existing facts that pertain to it at the time of its enunciation. Gradually the new theory becomes accepted and then acquires anomalies due to the new facts uncovered after its enunciation. That in turn generates a newer theory which elicits new techniques to test it and its predictions. These new techniques then uncover facts which eventually require further new theories and so on. The new theories are built on components of the old principles. It is said that each scientist stands on the shoulders of the giants who have gone before him. There can be no more honored place than to stand on the shoulders of Emil Fischer.