Sterically active binding sites

With regard to the s-BuNH2 results, it is likely that steric bulk, especially at the tertiary C-H alpha to the NH2 group, limits its ability to bind to the active catalyst site and therefore it cannot compete with EtgSiH, although it can still function as a reactant. 

Finally, a variety of alternative aromatic systems were evaluated in an effort to identify surrogates for the indole. Replacement by benzothiophene, indazole or substituted phenyl groups severely reduced or abolished activity in vitro, emphasizing the subtle electronic and steric factors governing the aromatic binding site (compounds not shown). 

Fig. 7.6. Topographical model of the active site of pig liver esterase showing the catalytic OH group and two binding sites (1 and 2) capable of accommodating hydrophobic groups of the substrate. Binding to site 1 is stronger and, thus, dominates until the steric dimensions of the site are exceeded. The model shows two substrates in position, namely dimethyl 3-methylglu-tarate (top) and dimethyl 3-benzylglutarate (bottom), which are hydrolyzed preferentially to the (R)- and (5)-monoester, respectively [68].

Non-competitive inhibitors. These inhibitors bind to the enzyme or the enzyme-substrate complex at a site other than the active site. This results in a decrease in the maximum rate of reaction, but the substrate can still bind to the enzyme. An analogous concept is that of allosteric inhibition. The site of binding of an allosteric inhibitor is distinct from the substrate binding site. In this case, the inhibitor is not a steric analog of the substrate and instead binds to the allosteric site (the phenomenon was termed thus by Monod and Jacob). 

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