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"The Enzyme and Substrate Must Fit Each Other Like a Lock and a Key" (1894)


In his paper "Einfluss der Configuration auf die Wirkung der Enzyme," Berichte der deutschen chemischen Gesellschaft 27 (1894) 2985-2993, German chemist Emil Fischer at the University of Berlin provided a structural interpretation of the selectivity of enzymes—their ability to discriminate among very similar molecules, confirming Pasteur's observations in fermentation of tartaric acid. Fischer wrote, “Only with a similar geometrical structure can molecules approach each other closely, and thus initiate a chemical reaction. To use a picture, I should say that the enzyme and substrate must fit each other like a lock and key.” (Quoted by Lesk, Protein Structure, 36).