Clostridium thermocellum (bacteria, thermophile)
The German biochemist Emil Fischer, at the end of the nineteenth century, proposed that enzymes and their substrates fit to each other like a lock and a key made for the lock. This hypothesis proved to be correct long before the three-dimensional structure of any chemical was known. While this may seem trivially obvious to us today, it was a very revolutionary idea at the time. Fischer got the second Nobel prize in chemistry, in 1902, not for this idea, but this concept is what made his name famous. As any good thief knows: if the key does not fit the lock, modify the key to make it fit. Nature has similar tricks. However changing the shape of the key, a small molecule, is often easy, since they may be flexible to begin with. What nature sometimes does, is change the lock, the protein to which a small molecule binds. That is a much less easy undertaking as it may require the large-scale movements of protein parts. When such a change happens, as a result of ligand-binding, it is called induced fit. Many natural chemical processes are driven by such large-scale changes. The structure here shows one example of such a change.
The structure shown here is a family 5 endoglucanase, which hydrolysis cellulose. The enzyme's job then is to cut the link between two neighboring sugar residues and is important in the digestion of large carbohydrate complexes. The barrel structures with 8 beta/alpha topology are often observed in glycosidase families. Seven amino acid residues located close to the catalytic reaction center are also strictly conserved in family 5 cellulases. Only three of these residues make direct contacts with the substrate, but all contribute to the stability of the active site architecture. Glu 140, one of the three residues, donate proton to the substrate and sits on a short loop whose orientation is changed significantly by the binding of sugars.
Protein Data Bank (PDB)
author: Arno Paehler