Its a very good question and i will try to answer it logically although i am not sure myself. Seeing the complexity of a single cell where we have a lot of proteins doing their respective work, cell needs to have specific enzymes for specific reactions. Now, if the active site is just outside and easy accessible, any substrate can interact with the active site to give some false response... on the other hand, if the active site is buried, only specific protein of particular size can go inside and reach the active site and then reaction can happen. I think that it has more implications from evolutionary point of view.
according to me if the active site is buried the substrate will be surrounded almost 360 degree by the protein permitting multiple S-E interactions which in turn will create a more effective transition state
Abstracted answer
The following data can be considered when the enzyme active site is buried:
(i) Protection of the active site from the surrounding environment in order to prevent water molecules to integrate the active site /or to keep a fixed water molecule number inside it (molecules required for substrate fixation and/or catalysis).
(ii) Only substrate interaction with the active site surface provokes a correct conformational change of the active site in order to accommodate the substrate molecule correctly: fixation and orientation against the active site catalyzing groups.
(iii) A correct accommodation of the substrate molecule leads to a rapid and correct chemical transformation (specific catalysis). By this way, substrate catalysis requires a relatively low level of activation energy. Furthermore, the whole enzyme reaction (substrate fixation, chemical transformation and product release) is exergonic or requires the lowest level possible of exchangeable energy (deltaG). The reaction is said thermodynamically favored.
Joseph Kreit
Thanx to Prof. joseph to gave such useful information regarding buried active site of enzyme....once again thanx a lot sir
Behind the points mentioned by Joseph, one of the most important aspects in enzyme catalysis is the change in the electrostatic molecular surface which surround the transition-state. This implies a exquisite orientation of local dipolar moments around the transition-state (TS) with strong impact in the stability of this theoretical species (true TSs cannot be observed, as by definition, their half lives are zero, reaction intermediates, can however be probed and through them the TS structures can be inferred). In this "selected" environment, the chemical groups have a restricted mobility, and frequently, these configuration has unfavorable free energy in the absence of the Substrate or the TS. This contrasts with chemical reactions in solution where the solvent around the reactant adapts to acquire a highly dynamical structure with minimal energy (free energy) i.e., solvent molecules orient to provide favorable interactions with the solute (low enthalpy), but with the smallest possible interference to the solvent continuous reorganization (high entropy). With basis on these concepts, enzymes have frequently be considered as TS supersolvents.
The more buried an active site, the higher the chance to provide and optimal environment for catalysis, however, a functional enzyme should provide a path for the reactants to reach the active site (AS) and products to leave. Therefore, AS accessibility is probably a compromise, reached throughout evolution, between a controlled "supersolvent", environment for the TS, with effective access to the substrates and products.
And additional point poorly considered in this analysis is the protein dynamics, which has also an important contribution, and is probably a relevant component of the selective pressures shaping the evolution of natural catalysts.
You can read more on this subject at:
1. García-Meseguer R , Martí S , Ruiz-Pernía JJ , Moliner V , & Tuñón I (2013) Studying the role of protein dynamics in an SN2 enzyme reaction using free-energy surfaces and solvent coordinates. Nat Chem 5(7):566--571.
2. Fried SD & Boxer SG (2013) Thermodynamic framework for identifying free energy inventories of enzyme catalytic cycles. Proceedings of the National Academy of Sciences 110(30):12271-12276.
3. Garcia-Viloca M , Gao J , Karplus M , & Truhlar DG (2004) How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations. Science 303(5655):186-195.
4. Lin P , Pedersen LC , Batra VK , Beard WA , Wilson SH , & Pedersen LG (2006) Energy analysis of chemistry for correct insertion by DNA polymerase β. Proceedings of the National Academy of Sciences 103(36):13294-13299.
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