From lock and key model to induced fit

From lock and key model to induced fit model Understanding how science works Victor Lau CUHK

Science model What you observed What you think it may be like that

Science model • A model in science is a simplified description and explanation of the natural process. • Sometimes model is used the same as theory in science. • The development of science model needs a little of imagination: You had not really seen a substrate binding to the enzyme!

In 1894, Fischer first used lock and key to explain the action of enzymes - lock and key model Group discussion • How is lock-key similar to enzyme action? • Would you liken enzyme to a lock or a key? Why?

• Lock-key model is a science model to explain the specificity of enzyme action. • However, lock-key model does not truly represent the real enzyme action, which would be more complex. • Fischer was creative to think of this model as he never directly saw how enzyme works!

Models ? • Do not mix up science model with physical model. • Scientific model is a concept, which can be represented in physical model, diagrams, mathematical formula, and even words. Lock and key model represented by diagram Lock and key model represented by physical model https: //www. youtube. com/watch? v=Sd. X 3 Rfkz-lk

Problems with lock and key model X Y Z Which substrate can bind with the enzyme? All can tightly bind with the enzyme, but only X will be catalyzed into product!

A new model - induced fit model In 1958, Koshland proposed an induced fit model to account for the problems. reaction !

Catalytic groups A and B are brought to the right locations to catalyze the substrate into products. Catalytic groups A and B cannot go to the right locations. So there is no catalysis of the substrate.

Induced fit model • Koshland likened the model to a hand in a glove. Why? ? • How is this model different from the lock-key model?

• Try to use the physical model provided to explain the induced fit model. https: //www. youtube. com/watch? v=Jknr. Dko. QF 1 E

Evidence for induced fit model? • Koshland needed to provide evidence to convince other scientists to accept this new model! • According to the hypothesis that enzyme can change its shape when bound by a substrate, he predicted that some chemical groups may be exposed by the binding. This would not be possible for a “rigid” enzyme in the lock-key model.

Initial evidence for induced fit model SH group hidden SH group is exposed after binding

Is the evidence convincing? “ The theory of Emil Fischer was deep in the hearts of scientists and journal editors, so I had great difficulty getting the original ideas published or convincing skeptics. . . “ Koshland 1994 Group discussion Are scientists all objective and rational?

More evidence • Other scientists “joined in” to provide more evidence. “ The findings from modern X-ray crystallography that essentially all enzymes undergo conformational changes induced by substrate binding has made the induced fit theory universally accepted in textbooks and by scientists. ” Koshland 1994 Group discussion • Why other scientists wanted and could “join in” ? • What made the induced fit model universally accepted in the end?

A journey of scientific discovery • 1894 - Fischer put forward the lock and key model. It was widely accepted for nearly 100 years. • 1958 – Koshland proposed induced fit model • 1970 s – Induced fit model widely accepted Group discussion • Do you think the induced fit model may be also found wrong in the future? • If science knowledge can change over time, is it reliable? Should we still believe in science?

Reference • Koshland, D. E. (1994). The Key-Lock Theory and the Induced Fit Theory. Angew. Chem. Inl. Ed. Engl. 33, 2375 -2378 • Koshland, D. E. (2004). Crazy, but correct. Nature, 432