Catalysis protein dynamics

Scrutton, N. S., Basran, J.. Sutcliffe, M. J. 1999 New insights into enzyme catalysis ground state tunnelling driven by protein dynamics. Eur. f. 

Tunneling assisted by protein dynamics 72 Tunneling as a contribution to catalysis prospects and problems 73 References 74... 

This is a subject in which the role of sophisticated theoretical work has been especially crucial aheady, and its importance continues to grow. The most controversial aspect of the subject is the question of whether and how protein vibrations are directly linked to the catalysis of hydrogen tunneling by enzymes. The full nature and value of the theoretical work is not covered in the present article, nor are the evidence and concepts that underlie proposals for the involvement of protein dynamics. It is our intention to follow the present article with a later treatment of the theoretical contributions and the dynamical questions. 

Protein Dynamics and Hydrogen Tunneling in Enzymatic Catalysis (from Kohen, 2002)... 

This article will describe the different chemical strategies used by enzymes to achieve rate acceleration in the reactions that they catalyze. The concept of transition state stabilization applies to all types of catalysts. Because enzyme-catalyzed reactions are contained within an active site of a protein, proximity effects caused by the high effective concentrations of reactive groups are important for enzyme-catalyzed reactions, and, depending on how solvent-exposed the active site is, substrate desolvation may be important also. Examples of acid-base catalysis and covalent (nucleophilic) catalysis will be illustrated as well as examples of "strain" or substrate destabilization, which is a type of catalysis observed rarely in chemical catalysis. Some more advanced topics then will be mentioned briefly the stabilization of reactive intermediates in enzyme active sites and the possible involvement of protein dynamics and hydrogen tunneling in enzyme catalysis. 

In conclusion, enzymes use a variety of strategies to achieve high rates of catalysis. Transition state stabilization seems to be the dominant factor in catalysis, but in some enzymes, the more sophisticated strategies such as substrate destabilization and protein dynamics seem to play an important role. 

Henzler-Wildman KA, Lei M, Thai V, Kerns SJ, Karplus M, Kern D. A hierarchy of timescales in protein dynamics is linked to enzyme catalysis. Nature 2007 450 913-916. Henzler-Wildman KA, Thai V, Lei M, Ott M., Wolf-Watz M, Fenn T, Pozharski E, Wilson MA, Petsko GA, Karplus M, Hubner CG, Kern D. Intrinsic motions along an enzymatic reaction trajectory. Nature 2007 450 838-U813. 

Entsch B, Cole LJ, Ballou DP. Protein dynamics in catalysis by flavoprotein hydroxylases. In Elavins and Elavoproteins. Nishino T, Miura R, Tanokura M, Fukui K, eds. 2005. ARchiTech, Tokyo, Japan, pp. 143-154. 

The interiors of proteins are more densely packed than liquids [181], and so the participation of the atoms of the protein surrounding the reactive system in an enzyme-catalysed reaction is likely to be at least as important as for a reaction in solution. There is experimental evidence which indicates that protein dynamics may modulate barriers to reaction in enzymes [10,11]. Ultimately, therefore, the effects of the dynamics of the bulk protein and solvent should be included in calculations on enzyme-catalysed reactions. Dynamic effects in enzyme reactions have been studied in empirical valence bond simulations Neria and Karplus [180] calculated a transmission coefficient of 0.4 for proton transfer in triosephosphate isomerase, a value fairly close to unity, and representing a small dynamical correction. Warshel has argued, based on EVB simulations of reactions in enzymes and in solution, that dynamical effects are similar in both, and therefore that they do not contribute to catalysis [39]. 

The Quantum Kramers Approach to Enzymatic Hydrogen Transfer - Protein Dynamics as it Couples to Catalysis... 

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