Influence of Configuration on the Action of Enzymes
An enzyme cleaves only the molecular shape it fits — like a key in a lock.
An enzyme is a lock that only one shape of key can open — and Fischer found two enzymes whose keys were mirror images of each other.
The big idea
Enzymes are the cell's tireless workers: each speeds up one particular chemical reaction and almost no other. Emil Fischer asked the obvious, hard question — out of the thousands of molecules around it, how does an enzyme pick the single one it is meant to work on?
He built two sugars that were chemically identical except for the three-dimensional arrangement at one carbon — as alike, and as different, as your left and right hands. Then he handed them to two enzymes. Each enzyme seized only its matching "hand" and split it apart; the mirror-image sugar it ignored completely. The enzyme, in other words, was not reading the chemical formula. It was feeling the shape.
How it came about
By 1894 Fischer was the world's master of sugar chemistry. He had spent a decade painstakingly working out the exact three-dimensional shapes of the sugars — the achievement that would win him the 1902 Nobel Prize — so he was perfectly placed to make two molecules that differed by the smallest possible twist.
He took invertin, an enzyme from yeast, and emulsin, an enzyme from bitter almonds, and tried each on his two near-twin glucosides. Invertin attacked one form and not the other; emulsin did the exact opposite. To capture what he had found, Fischer reached for a homely image that has stuck ever since: enzyme and substrate must fit together "like lock and key."
Why it mattered
This is the seed of molecular recognition — the realisation that life works because molecules know one another by shape. It is why your body can run thousands of precise reactions without their interfering, and it is the founding idea behind modern medicine: nearly every drug is designed as a key, cut to fit one particular protein lock and as few others as possible.
A way to picture it
Think of a key and its lock. A key that is a hair's-breadth wrong — say, the mirror image of the right one — will slide partway in and then jam, opening nothing. Fischer's two sugars were exactly such mirror-image keys, and his two enzymes were the matching locks: each turned for one key only. A left glove on a right hand makes the same point — same fingers, same size, and still it will not fit.
Where it sits
Decades earlier Pasteur had noticed that living things prefer one mirror-form of a molecule over the other, but no one knew why. Fischer turned that hint into a mechanism: recognition by shape. His static lock was later given a flexible hinge by Koshland's "induced fit" (1958), and his binding step was made quantitative by Michaelis and Menten's kinetics in 1913 (also in this Library). From those two sugars runs a straight line to all of structural biology and to today's structure-based drug design.
Um ein Bild zu gebrauchen, will ich sagen, dass Enzym und Glucosid wie Schloss und Schlüssel zueinander passen müssen, um eine chemische Wirkung aufeinander ausüben zu können.