Inhibitor binding kinetic aspects

Research in this field is ongoing aiming to understand the mechanism of action of kinetic inhibitors. Lee and Englezos (2005) showed that inclusion of polyethylene oxide (PEO) to a kinetic inhibitor solution was found to enhance by an order of magnitude the performance of the hydrate inhibitor. Binding of inhibitor molecules to the surface of hydrate crystals was considered to be the key aspect of the mechanism of kinetic inhibition (Anderson et al.,... 

The non-competitive and uncompetitive modes of inhibition described above are special cases that in practice arise very rarely in these simple forms. In reality, the situation is usually more complex in that inhibitors bind with differing affinities to the free and substrate-bound forms of the enzyme, and also the ternary EIS complex may be able to undergo catalysis, albeit at a lower rate. These circumstances define what is called mixed inhibition, which is less easy to characterise since the kinetic behaviour and equations are much more complex. The reader is referred to Cor-nish-Bowden (1995) for a comprehensive and authoritative account of this and other aspects of enzyme kinetics. 

Electrons are transferred by the respiratory electron chain to a cytochrome b which then donates electrons to the Mo-protein (nitrate reductase). By using reduced viologens it should be possible to determine the kinetics of nitrate reduction by the nitrate reductase however, no information on this aspect is currently available. The sensitivity of nitrate reduction to inhibition by cyanide is considered to be due to association of the inhibitor with molybdenum residues in the nitrate reductase (Enoch and Lester, 1975). Cytochrome b involved in nitrate reduction does not bind cyanide. 

In this section we briefly review experimental and computer modeling aspects of several important pFI-dependent properties of proteins. In the computer modeling part, we focus on employing computed pfC s for the prediction of these properties. With this in mind, we start with the pH dependence of the binding of inhibitors to enzymes, which is closely related to the determination of pK s by pH-dependent kinetics methods described in the preceding section. 

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