Enzyme specificity

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Pictographic representation of an enzymatic conversion. The specific active centers are shown here in a simplified manner by means of geometric figures.

The term enzyme specificity or substrate specificity describes the phenomenon that enzymes can usually only take up one substrate or a limited number of substrates in their active center , which describes one aspect of the key and lock principle . This fact is of fundamental importance both for the organism that has these enzymes and for science.

Factors of specificity

Enzymes are usually very limited in the number of substrates that they can bind. This is justified by the necessary complementarity between the substrate and the active center of the enzyme. A distinction is made between two aspects:

Geometric complementarity

The stereochemical point of view is meant here, since the active center of an enzyme is only accessible to substrates of a certain shape and size, especially since there is no repulsion between the amino acid residues in the active center and the substrate, for example, when the van der Waals radii are not reached may, so that not only the shape of the substrate, but in most cases also the functional groups that form the shape of the substrate, are important for the geometric complementarity.

Electronic complementarity

The electrostatic interactions between the active center and the substrate are also of great importance when they are bonded to one another. Hydrogen bonds , dispersion forces and dipole-dipole interactions are increasingly formed . All of these intramolecular forces are responsible both for the uptake of the substrate in the active center and for the stabilization of the substrate in the same. It is even more rare that covalent bonds are formed between amino acid residues of the enzyme and the substrate for the purpose of stabilization.

Such interactions also induce the conformational adaptation of the active center of an enzyme to the substrate, which is referred to as “ induced fit ”. This phenomenon is also a reason for the mostly high specificity of enzymes, since the induced fit initiates the enzymatic conversion. There are substrates that can be taken up in the active center of an enzyme, but do not have complete electronic complementarity due to a different orientation or arrangement of functional groups, so that a substrate-induced adaptation of the active center - which is relevant for the conversion - does not occur.

Both complementarities and thus also the enzyme specificity are ultimately dependent on the tertiary and quaternary structure of the active center of an enzyme.

Argininosuccinate lyase binds argininosuccinate in its active center

Types of specificity

An effect specificity describes the type of chemical reactions catalyzed by an enzyme caused by the structure of the enzyme, e.g. B. hydrolases , hydroxylases , synthases . It is relatively rare that an enzyme can only bind one substrate. Many enzymes are able to bind more than just one substrate. There are several subdivisions for this phenomenon:

Substrate specificity

It seldom happens that an active center of an enzyme can actually only bind one specific substrate. A substrate specificity comes with enzymes such. B. horseradish peroxidase (HRP), maltase-glucoamylase , all RNases and restriction enzymes .

Group specificity

The largest proportion of biologically active enzymes belong to this category. Most enzymes do not take up the substrates (mostly molecules and molecular ions ) as a whole in the active center, but only the parts of the substrates that have to be converted. It is therefore also possible that the molecular structures of the substrates that are outside the enzymatically relevant areas can vary greatly up to a certain extent. This limitation of the variability is due to the fact that substrate structures that are outside the active centers can sterically and electrostatic interactions distort the enzyme structure, whereby the activity of the enzyme is weakened or even canceled.

The enzyme only binds part of the substrate (cavity model) in its active center.

However, the substrates of enzymes whose active centers completely take up the respective substrates can also vary to a greater or lesser extent. This is possible if the functional groups of the various substrates of an active center have similar physical properties, such as polarities and bond lengths .

It is not uncommon for enzymes to have a so-called group specificity, which implies that their active centers can bind substrates, some of which have a wide variety of structures, which only have the same arrangement of individual functional groups . This suggests that the active center only binds the molecular structures in the area of ​​the invariable functional groups. An example of this is alcohol dehydrogenase , which can bind and convert both methanol , ethanol and - albeit significantly weaker - higher alkanols .

Although an enzyme can have several possible substrates for the same active site, the respective activity of the enzyme is always different for different substrates. Because despite the complementarity of all substrates, they usually differ in the effectiveness of their implementation. For example, when using different substrates at the same active site of an enzyme, the reaction rate can vary. That is why there is always a substrate for enzymes that is most effectively converted, as has already been shown with alcohol hydrogenase, the most effective substrate of which is methanol.

Stereospecificity

Most enzymes are so specific that they can only take up one enantiomer of the substrate, since the substituents of the enantiomer of a substrate do not attack at the same sites in the active center of the corresponding enzyme as the primary substrate, which results in weaker binding or complete non-uptake . The Pfeiffersche rule describes the relationship between the affinity and the enantioselectivity between an enzyme and a chiral substrate.

Importance to science

pharmacology

Almost all effective drugs are based in their functionality on the binding and the consequent inhibition or activation of proteins, which also include the enzymes. This is also a central task of pharmacology , since substances usually have to be synthesized that are able to bind specifically to a very specific enzyme in order to influence its functionality.

biochemistry

In biochemistry , too, it plays a major role that enzymes can only convert certain substances. There they mostly act as laboratory tools. For example, sequencing a genome requires small DNA sequences . In order to break up the biologically active DNA, which consists of around 3.2 billion base pairs , into smaller DNA fragments of a few 100 base pairs in size, restriction enzymes are used that are capable of breaking the DNA at specific nucleotide sequences and at special ones Way to "cut up". Due to a lack of specificity, such enzymes can carry out their hydrolysis at other points in the DNA than their recognition sequence usually limits. This can e.g. B. can be caused by suboptimal environmental conditions in terms of tonicity and a lack of cofactors . Changing enzyme specificity is a goal of protein engineering .

Analytics

The task of analytical chemistry is often to detect organic and sometimes high-molecular substances. However, since proteins to be detected, for example, can accommodate a large number of chemical groups, this task can hardly be solved using classical analytical methods . Due to the specificity of enzymes, however, it is possible to detect a very specific substance with a high degree of probability. This probability depends on the number of substrates to which the selected enzyme can also bind. A well-known use of this method is the GOD test , which can be used to detect glucose (for example in urine ). The enzyme glucose oxidase is used, which specifically oxidizes glucose to glucono-δ-lactone . The resulting by-product hydrogen peroxide initiates a characteristic coloration by another enzyme ( peroxidase ) that binds specifically to peroxides .

See also

literature