Enzyme catalytic mechanism

I n chapter 7 we saw that enzymes can increase the rates of reactions by many orders of magnitude. We noted that enzymes are highly specific in the reactions they catalyze and in the particular substrates they accept. In this chapter we explore the mechanisms of several enzyme-catalyzed reactions in greater detail. Our goal is to relate the activity of each of these enzymes to the structure of the active site, where the functional groups of amino acid side chains, the polypeptide backbone, or bound cofactors must interact with the substrates in such a way as to favor the formation of the transition state. We explore enzyme catalytic mechanisms in many subsequent chapters as well but usually in less detail than here. 

The examples in this section have been chosen to provide an in-depth presentation showing how RSSF currently has been applied to the study of biological systems. These applications include the study of isotope effects on enzyme-catalyzed reactions, the investigation of substrate-metal ion interactions in metalloenzymes, the search for and identification of covalent intermediates in enzyme-catalyzed processes, the analysis of the effects of site-directed mutations on enzyme catalytic mechanism, and the exploitation of natural and artificial chromophores as probes of allosteric processes. 

The small molecule examples discussed in this review provide a rich collection of data pertaining to the catalytic functions which zinc ion can perform as an electrophile in aqueous solution. The high resolution structural information on the zinc-metalloproteins together with information derived from chemical modifications, kinetic studies, and other spectroscopic techniques place severe constraints on the possible roles played by zinc ion in enzyme catalytic mechanism. As a consequence, the focus of this review is placed on the relationship of these... 

A variety of techniques have been applied to investigate enzyme reaction mechanisms. Kinetic and X-ray crystallographic studies have made major contributions to the elucidation of enzyme mechanisms. Valuable information has been gained from chanical, spectroscopic and biochemical studies of the transition-state structures and intermediates of enzyme catalysis. Computational studies provide necessary refinement toward our understanding of enzyme mechanisms. The ability of an enzyme to accelerate the rate of a chemical reaction derives from the complementarity of the enzyme s active site structure to the activated complex. The transition state by definition has a very short lifetime ( 10 s). Stabilization of the transition state alone is necessary but not sufficient to give catalysis, which requires differential binding of substrate and transition state. Thus a detailed enzyme reaction mechanism can be proposed only when kinetic, chemical and structural components have been studied. The online enzyme catalytic mechanism database is accessible at EzCatDB (http //mbs.cbrc.jp/EzCatDB/). 

CGTase is a kind of glycoside hydrolases, and according to the deference in the conformation of the anomeric carbon atom of glycosidic bonds subjected to hydrolysis, there are two kinds of enzyme catalytic mechanisms One is conformation inversion type (Fig. 2.2(a)), and the other is conformation keeping... 

Immobilized enzyme reactors are increasingly popular due to their advantages over conventional catalysts. For efficient reactor design and performance prediction, quantitative knowledge of reaction kinetics and the factors affecting them is required. In this chapter, enzyme catalytic mechanisms are described and the kinetic models developed from these mechanisms are discussed. The chapter also discusses the kinetics of immobilized enzymes and their related mass transfer effects. Diffusion restrictions are described with a particular focus on packed bed reactors. The chapter concludes with a brief discussion of immobilized enzyme reactor design and scale-up. 

In this chapter, mechanism-based inhibition is discussed in its broadest sense, where an inhibitor is converted by the enzyme catalytic mechanism to form an enzyme-inhibitor complex. Other terms used in the literature for mechanism-based inhibitors include suicide inhibitors, suicide substrate inhibitors, alternate substrates, substrate inhibitors, and enzyme inactivators, as well as irreversible, catalytic, or cat inhibitors. The terms alternate substrate inhibition and suicide inhibition are used here to describe the two major subclasses of mechanism-based inhibition. 

One of the most promising approaches for elucidation of enzyme catalytic mechanisms and designing new catalysts is a directed evolution , method of purposeful mutation of non-enzymatic proteins to evolve desired activity mimicking native enzymes. Another important trend in chemical and oizyme catalysis is the growing role of theoretical calculation of thermo mamic parameters of enzyme reactions, conqniter analysis of X-ray structural models, taking from Data Base, computer modeling of structure of chemical catalysts and enzymes and their interaction with substrates and inhibitors, and theoretical construction of transition and pretransitim states of reactions of interest. 

Bugg TDH. Dioxygenase enzymes catalytic mechanisms and chemical models. Tetrahedron 2003 59 7075-7101. 

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