Enzymatic steering

Siebert, M. R. Zhang, J. Addepalli, S. V. TantiUo, D. J. Hase, W. L. The need for enzymatic steering in abietic acid biosynthesis Gas-phase chemical dynamics simulations of carbocation rearrangements on a bifurcating potential energy surface, J. Am. Chem. Soc. 2011,133, 8335-8343. 

Partial lipid extraction is considered as biologically important in several processes involving membranes, for example the fusion of membranes or enzymatic reactions with participation of phospholipids. To simulate this process, non-equilibrium or steered MD simulations can be used. This type of simulation was employed for the first time by Grubmuller et al. [96] to study the rupture of the binding in the strepta-vidin-biotin complex. Inspired by this pioneering work, similar studies have been undertaken to characterize the extraction of a phospholipid from the membrane. 

Approximation and orientation This is the entropic contribution (Page, 1977). Enzymatic reactions take place in the confines of the enzyme-substrate complex. The catalytic groups are part of the same complex as the substrate. This proximity/propinquity and appropriate positioning of substrate molecules with respect to the catalytic groups in the active site via stereopopulation control or orbital steering may contribute to a rate enhaucement with a factor of 10 to 10. ... 

In solution the intramolecular coordination of the nucleotide function to the lower a-axial coordination site of the corrin-bound cobalt center of complete corrins occurs with Httle build-up of strain [149]. This allows the (coordinating) nucleotide to steer the reactivity, as well as the face-selectivity, of certain organometalUc reactions involving the corrin-boimd cobalt center [75]. Experiments by Eschenmoser demonstrated that cobal-amins can self-constitute in solution from the Bi2-nucleotide portion and incomplete cobyrinic acid derivatives to show a remarkable kinetic and thermodynamic preference for the specific formation of the B 12-structure, and to a pre-enzymatic origin of the basic structural elements of the complete corrins [149]. 

One of the most common comparisons involves supra-molecular capsules and enzymes because they share many behaviors, properties, and common features. Encapsulation phenomena reveal new concepts that clearly show interaction between substrates and enzymes in the formation of active complexes that subsequently lead to catalytic reactions and product formation. Encapsulation criteria, and the relative driving forces involved, teach about substrate selectivity typical of enzymatic reactions, therefore the future development of new self-assembled capsules and the study of their encapsulation phenomena represents a test bench to master molecular recognition. Supramolecular capsules have already acted as supramolecular catalysts that are able to accelerate chemical transformation and to steer product selectivity, but turnover ability is still the critical point that requires improvements. 

Several key factors in enzymatic catalysis include their activity, stability, substrate concentration and temperature. Optimization of these factors will steer the enzyme towards the desired activity. Media pH was shown to affect the ionizable groups at the active site of the enzyme. Gangoiti et reported that P(3HO) depolymerase showed its maximum activity at pH 9.5 and a temperature of 40 °C. 

Peplowski, L., Kubiak, K., 8c Nowak, W. (2008). Mechanical aspects of nitrile hydratase enzymatic activity. Steered molecular dynamics simulations of Pseudonocardia thermophila JCM 3095. Chemical Physics Letters, 467,144. 

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