Extraneous site inhibitors

Extraneous Site Inhibitors. This type of inhibitor is the most recently recognized category. Very tight binding can be achieved with extraneous site inhibitors. They are named extraneous site inhibitors because they do not structurally resemble substrates, cofactors, or allosteric effectors and they bind either entirely, or to a large extent, to some site outside of or extraneous to the enzyme active site (9). 

The best characterized extraneous site ir bitors are the many chemical classes of herbicidal inhibitors of acetolactate synthase. These have been extensively reviewed elsewhere (i, 8,9,52,56,81,92). Extraneous site inhibitors are also exemplified by four classes of grass selective herbicides the aryloxyphenoxypropionic acids represented by diclofop, the cyclohexanediones typified by clethc m (for a recent review see (57)), the triazinediones (82) and the perhydroindolizinediones (83) (Figure 7). The following discussion is limited to the first two classes. Both classes of herbicides are potent, reversible inhibitors of acetyl-CoA carboxylase (ACC) from susceptible plants, the putative rate limiting enzyme in lipid biosynthesis. With wheat... 

Figure 7, Examples of extraneous site inhibitors of acetyl-CoA carboxylase.

Probably, the intrinsic calcium is important for maintaining the protein in an active conformation (about 5 calcium atoms are present per molecule molecular weight, 750,000 calculated for 275 y of calcium/g. of enzyme), and extraneously added calcium is bound near the active site, thus blocking it, or reacts with one of the groups on the active site. The inhibition is instantaneous and of non-< ompetitive character, with an inhibitor constant (Ki) of 5.3 X 10 M at 20° and pH 7.6 (compare the non-competitive inhibition by beryllium with Ki = 2.9 X 10 Af under the same conditions). 

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