In early biochemistry subjects proteins (enzymes) are described as catalytic switches. With their on/off modes corresponding to whether they are occupied by a substrate or unoccupied. The conformation of the protein was suited to find its one specific substrate, and accordingly the substrates would fit into the protein like a key into a lock. This ‘lock and key’ mechanism implies that the protein would be held in the static ‘lock’ conformation waiting for its substrate.
However when considering the Boltzmann distribution it seems unlikely that a protein (consisting of many individual molecules) could remain in a fixed position. In fact it is known that proteins can exist in many different structures and depend on many different parameters outside of their substrates. But if proteins can have a vast number of conformations how do they perform their highly specific functions? Section 9.6.3 of the text gives an interesting viewpoint: within a bulk sample of the myoglobin protein there are many different ‘conformational substates’ (shown by R. Austins experiment, figure 9.13). These substates are able to perform the overall protein function of binding oxygen, but they each have slightly different binding affinities due to their structural differences. Thus proteins are able to satisfy the Boltzmann distribution while still maintaining their function. However in regard to the lock and key fit, proteins are not so easily typified. In this context the proteins would be more aptly described as the lockpicker’s toolkit.
You're right; the 'static lock' model of a protein is a bit too simplistic. A more accurate model would be that in the energy minimisation surface that the protein is randomly walking along, the global minimum has another similarly sized local minimum nearby, separated by a small energy barrier. These two minima represent the two states of the protein, the locked and unlocked states. At any given moment, the protein is randomly moving around the minimum it is in, but doesn't have the energy to spontaneously move from one minimum to the next without the key molecule binding or dissociating.
ReplyDeleteSo there is still a Boltzmann distribution for the conformation of the protein, but the Boltzmann distributions of each state don't necessarily overlap (at least not at physiological temperatures.)
From other courses on enzymes, we learn that there are also other forms of enzyme-substrate binding. As you've mentioned, there is the classic "lock and key" hypothesis, where the substrate can just lock itself into the enzyme binding site. Another way is through "induced fit" whereby the substrate binds to an enzyme, though not in the optimal fit. However, the binding does force the enzyme binding site to undergo a conformation change to create that perfect fit. Finally, another type is known as "pre-equilibrium" in which the enzyme first undergoes a conformational change, and then the substrate can bind.
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