Structural Biochemistry/Protein function/Transition-state Model
Theory edit
The transition state of any reaction is difficult to study, because it has no visible lifetime. To understand the transition-state Model of enzymatic catalysis, the interaction between the enzyme and this transition in the course of a reaction needs to be understood. An enzyme is complementary to the transition state can be viewed as a requirement for catalysis. The energy "hill" that the transition state sits is what the enzyme must lower if catalysis is to occur. Since if it is too high, the reaction cannot take place. The idea of enzyme-transition state complementarity is shown through a variety of examples.
The structure of the transition state is basically an expanded and spelled out version of an original state where tertiary and secondary structures form concurrently. The transition state model is similar to another model which is known for folding proteins rather than providing a framework model, the "global collapse model". This is a possible common function feature for proteins missing the transition state. An example of the transition state model in action is the folding of barnase. Although barnase has formed complete secondary and tertiary elements in the transition state, a framework process was involved. Unfortunately, the framework could be tampered with by the global collapse model and a unified folding scheme could be presented.
Basics edit
The transition-state model starts with an enzyme which then binds to a substrate. Energy is the required to change the shape of substrate. Once the shape is changed, the substrate is unbound from the enzyme. This ultimately causes a change in the shape of the enzyme. One of the most important aspects of the model is that it increases the amount of free energy.
Explanation edit
The Transition State Theory is probably the most important rate enhancing mechanism to understand in regards to enzymes. This theory is stating that enzyme binds the transition state of the reaction more tightly than either the substrate or product which is causing the ΔG to be lowered. The weak interactions between the enzyme and substrate are optimized in the transition state.
There is a few important topics to note. If the active site of the "enzyme" is complementary to the substrate, then ΔG is raised. The “enzyme” does not enhance the reaction and stays bound. If the active site is complementary to the transition state, then ΔG is lowered and the enzyme enhances the reaction. ΔG for forming the transition state is favored by the energetics of weak interactions between the enzyme and the transition state.
The enzyme stabilizes and reduces the energy of the transition state structure by forming a non covalent bonds to it . The lowering of energy that results from the binding of the transition state increases the likelihood that the transition state will form and convert to the product. Transition-state stabilization is important to enzyme catalysis. As proof that the active site is most complementary to the transition state structure, chemicals known as transition-state analogs, which resemble the structure of the transition state, have been shown to bind to enzymes with higher affinity than substrates. Due to tight binding, many of these molecules are good inhibitors of enzymes. For example, the antibiotic, penicillin, inhibits the transpeptidase enzyme that catalyzes cross-linking of bacterial cell wall because it resembles the transition state for this reaction. It makes sense that enzymes are more complementary to the transition state than to their substrates. If they were most complementary to the substrate, they might bind them so tightly that the reaction would not be able to proceed.
Sources edit
Nelson, David L.; Cox, Michael M. (2005), Principles of Biochemistry (4th ed.), New York: W. H.
D E Otzen, L S Itzhaki, N F elMasry, S E Jackson, and A R Fersht. "Structure of the transition state for the folding/unfolding of the barley chymotrypsin inhibitor 2 and its implications for mechanisms of protein folding". http://www.pnas.org/content/91/22/10422.short. Last accessed: 30 Nov. 2011.