Solvation enzyme catalysis

In the 1950s, the push-pull mechanism whereby a proton is donated by one centre and received at another was considered as a major contributor to enzyme catalysis and to give rise to third-order terms in non-enzymic reactions. Third-order terms were observed in organic solvents but in water they are of minor importance because of the solvating power of this solvent for ions and polar centres. 

In an investigation of the role of water in enzymic catalysis. Brooks and Karplus (1989) chose lysozyme for their study. Stochastic boundary molecular dynamics methodology was applied, with which it was possible to focus on a small part of the overall system (i.e., the active site, substrate, and surrounding solvent). It was shown that both structure and dynamics are affected by solvent. These effects are mediated through solvation of polar residues, as well as stabilization of like-charged ion pairs. Conversely, the effects of the protein on solvent dynamics and... 

In the first reaction, intramolecular attack by the hydroxyl on the carboxyl carbonyl proceeds 5 X 108 times faster than the corresponding inter-molecular process (2). In the second reaction, the rate increases 107-fold upon switching the solvent from methanol to dimethylformamide (3). Obviously, the huge rate increases in these organic systems do not necessarily prove that similar effects are at work in enzymes. But to be suspicious is quite natural, and many people, too numerous to mention, have pointed out the possible relationship between enzyme catalysis and intramolecularity or solvation effects. 

AV Levashov, NL Klyachko, NG Bogdanova, K Martinek. FEBS Lett 268 238-240, 1990. NG Bogdanova. Enzyme Catalysis in Surfactant Reverse Micellar Systems Solvated with Water-Organic Solvent Mixtures. PhD dissertation, Moscow State University, Russia, 1989. NL Klyachko, S Merker, K Martinek, AV Levashov. Dokl Akad Nauk SSSR (Russ) 298 1479-1481, 1988. 

In analyzing the origin of enzyme catalysis, Warshel and others have advocated the importance of comparing the enzymatic reaction with a reference reaction in water [32]. In addition, it is also necessary to study the reference reaction in the gas phase in order to understand the intrinsic reactivity and the effect of solvation. Thus, to understand enzyme catalysis fully, we must compare results for the same reaction in the gas phase (intrinsic reactivity), in aqueous solution (solvation effects), and in the enzyme (catalysis). This is not possible when there is no model reaction for the uncatalyzed process in the gas phase and in water, or if the uncatalyzed reaction is a bimolecular process as opposed to a unimolecular reaction in the enzyme active site. None of these problems apply to the ODCase reaction. Furthermore, OMP decarboxylation is a unimolecular process, both in water and the enzyme, providing an excellent opportunity to compare directly the computed free energies of activation [1] this is the approach that we have undertaken [16]. Warshel et al. used an ammonium ion-orotate ion pair fixed at distances of 2.8 or 3.5 A as the reference reaction in water to mimic an active site lysine residue [32]. 

Non-covalent interactions govern phenomena related to condensation, solvation, adsorption, and crystallization. A role of non-covalent interactions in biology spans from controlling of protein folding and functions of nucleic acids to drug design, molecular recognition, and enzyme catalysis. 

G3(MP2)-RAD level calculations in the gas phase, in water using the CPMP solvation model, and in water with LinA or LinB enzyme catalysis have been used to investigate the decomposition of three hexachlorocyclohexane isomers. Although the a- and y-hexachlorocyclohexanes react by an E2 mechanism in the gas phase, in water and with LinA enzyme catalysis, the /3-hexachlorocyclohexane reacts by an 5 2 mechanism in the gas phase and with LinB enzyme catalysis, but by an ElcB mechanism in water. The reaction rates for all three isomers are enzyme water Th results are consistent with experimental observations. 

The rate enhancements accompanying intramolecular reactions when compared to related intermolecular counterparts have withdrawn the attention of several investigators in recent years not only for the phenomenon per se but also because the factors involved have close connections with the mechanism of enzyme catalysis. Out of the possible factors involved in enhanced intramolecular reactivity, changes in solvation of the reacting species and/or transition state in going from the intermolecular over to the intramolecular process have been taken into account from time to time. 

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