Specificity of enzymes

The binding of substrates to enzymes involves interactions between the substrates and reactive groups of the amino acid side-chains that make up the active site of the enzyme. This means that enzymes show a considerable specificity for the substrates they bind. Normally, several different interactions must occur before the substrate can bind in the correct orientation to undergo reaction, and binding of the substrate often causes a change in the shape of the active site, bringing reactive groups closer to the substrate.

Figure 2.3 shows the active sites of three enzymes that catalyse the same reaction — hydrolysis of a peptide bond in a protein (section 4.4.3). The three enzymes show different specificity for the bond that they hydrolyse:

  • Trypsin catalyses cleavage of the esters of basic amino acids.
  • Chymotrypsin catalyses hydrolysis of the esters of aromatic amino acids.
  • Elastase catalyses hydrolysis of the esters of small neutral amino acids.

This difference in specificity for the bond hydrolysed is explained by differences in the substrate binding sites of the three enzymes. In all three enzymes, the substrate binds in a groove at the surface, in such as way as to bring the bond to be cleaved over the serine residue that initiates the catalysis. The amino acid providing the carboxyl side of the peptide bond to be cleaved sits in a pocket below this groove, and it is the nature of the amino acids that line this pocket that determines the specificity of the enzymes:

Figure 2.3 Enzyme specificity — the substrate binding sites of trypsin, chymotrypsin and elastase.





CH3 L-alanine

Figure 2.4 DL-isomerism.

In trypsin there is an acidic group (from aspartate) at the base of the pocket — this will attract a basic amino acid side-chain.

In chymotrypsin the pocket is lined by small neutral amino acids, so that a relatively large aromatic group can fit in.

In elastase there are two bulky amino acid side-chains in the pocket, so that only a small neutral side-chain can fit it.

The specificity of enzymes is such that they distinguish between the d- and l-isomers (Figure 2.4), and between the cis- and trans-isomers (Figure 2.5 and section, of the substrate. This is because the isomers have different shapes. In non-enzymic chemical reactions they may behave identically, and it may be difficult to distinguish between them. The shape and conformation of the substrate are critically important for binding to an enzyme.

The participation of reactive groups at the active site provides specificity not only for the substrates that will bind, but also for the reaction that will be catalysed. For example, in a non-enzymic model system, an amino acid may undergo a-decarboxylation to yield an amine, transfer of the a-amino group and replacement with an oxo-group (section, isomerization between the d- and l-isomers, or a variety of reactions involving elimination or replacement of the side-chain. In an enzyme-catalysed reaction only one of the possible reactions will be catalysed by any given enzyme.

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