Enzyme dynamics

Ovadi, J. (1988). Old pathway—new concept Control of glycolysis by metabolite-modulated dynamic enzyme associations. Trends Biochem. Sci. 13,486-490. 

In specific situations of cells, e.g., during cell cycle progression and differentiation, the methylation pattern can be quite dynamic. Enzymes have been identified that function as demethylases and can alter the methylation pattern. Furthermore, DNA methylation has been recognized as an important aspect of tumorigenesis. Changes in the methylation pattern have been linked in many tumors to decreased expression of tumor suppressor genes (see Chapter 14). 

Ha T, Ting A Y, Liang J, Caldwell W B, Deniz A A, Chemla D S, Schultz P G and Weiss S 1999 Single-molecule fluorescence spectroscopy of enzyme conformational dynamics and cleavage mechanism Proc. Natl Acad. Sc/. USA 96 893-8... 

R. C. Wade, M. E. Davis, B. A. Luty, J. D. Madura, and J. A. McCammon. Gating of the active site of triose phosphate isomerase Brownian dynamics simulations of flexible peptide loops in the enzyme. Biophys. J., 64 9-15, 1993. 

Our work is targeted to biomolecular simulation applications, where the objective is to illuminate the structure and function of biological molecules (proteins, enzymes, etc) ranging in size from dozens of atoms to tens of thousands of atoms today, with the desire to increase this limit to millions of atoms in the near future. Such molecular dynamics (MD) simulations simply apply Newton s law to each atom in the system, with the force on each atom being determined by evaluating the gradient of the potential field at each atom s position. The potential includes contributions from bonding forces. 

Fig. 7.15 The variation in torsion angles can be effectively represented as a series of dials, where the time corresponds to the distance from the centre of the dial. Data from a molecular dynamics simulation of an intermolecular complex between the enzyme dihydrofolate reductase and a triazine inhibitor [Leach and Klein 1995].

Pretreatment of membranes with dynamically formed polarization layers and enzyme precoats have been effective (12,13,39). Pretreatment with synthetic permeates prevents startup instabiUty with some feed dispersions. 

Protein dynamics—the action of enzymes and molecular motors—provides the key to understanding the biochemistry of this cheetah and the grasses through which it runs. (Frank Lane/Parfitt/Tony Stone Images)... 

The interpretations of Michaelis and Menten were refined and extended in 1925 by Briggs and Haldane, by assuming the concentration of the enzyme-substrate complex ES quickly reaches a constant value in such a dynamic system. That is, ES is formed as rapidly from E + S as it disappears by its two possible fates dissociation to regenerate E + S, and reaction to form E + P. This assumption is termed the steady-state assumption and is expressed as... 

It has been frequently suggested that dynamical factors are important in enzyme catalysis (Ref. 9), implying that enzymes might accelerate reactions by utilizing special fluctuations which are not available for the corresponding reaction in solutions. This hypothesis, however, looks less appealing when one examines its feasibility by molecular simulations. That is, as demonstrated in Chapter 2, it is possible to express the rate constant as... 

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