Lock-and-key theory

The problem of molecular recognition has attracted biologically oriented chemists since Emil Fischer s lock-and-key theory l0). Within the last two decades, many model compounds have been developed micelle-forming detergents11, modified cyclodextrins 12), many kinds of crown-type compounds13) including podands, coronands, cryptands, and spherands. Very extensive studies using these compounds have, however, not been made from a point of view of whether or not shape similarity affects the discrimination. 

In terms of the carbanion equivalent, the enolase superfamily has a strong relation with decarboxylation reaction. This family is characteristic in its promiscuity. If one is reminded of the phrase lock and key theory for the relation between the substrate and the enzyme, the word promiscuity of the enzyme may be unbelievable. However, in addition to natural promiscuity, we can change the enzyme to be promiscuous by introducing mutation, especially in the case of the enolase superfamily. This will be one of the challenging problems in future. For that purpose, biotechnology and informatics skill will be essential tool in addition to precise analysis of the reaction mechanism. 

Impressed by the specificity of enzymatic action, biochemists early adopted a "lock-and-key" theory which stated that for a reaction to occur the substrate must fit into an active site precisely. Modem experiments have amply verified the idea. A vast amount of kinetic data on families of substrates and related competitive inhibitors support the idea and numerous X-ray structures of enzymes with bound inhibitors or with very slow substrates have given visual evidence of the reality of the lock-and-key concept. Directed mutation of genes of many enzymes of known three-dimensional structure has provided additional proof. 

Lobry de Bruyn-Alberda van Ekenstein transformation 693 Lock and key theory 478 Log phase of growth 470 Lon protease 628 Loricin 439... 

One of the original theories to account for the formation of the enzyme-substrate complex is the "lock and key" theory. The main concept of this hypothesis is that there is a topographical, structural compatibility between an enzyme and a substrate which optimally favors the recognition of the substrate as shown in Figure 2.3. 

Fischer s Lock and Key Theory (Rigid Template Model)... 

Much less is known about the first interaction between ligand and receptor. It seems to become clearer and clearer that the productive lock and key theory needs some adjustment. Receptors are dynamic molecules, being able to adapt several conformations. 

An enzyme is typically a large protein molecule that contains one or more active sites where interactions with substrates take place. These sites are structurally compatible with specific substrate molecules, in much the same way as a key fits a particular lock. In fact, the notion of a rigid enzyme structure that binds only to molecules whose shape exactly matches that of the active site was the basis of an early theory of enzyme catalysis, the so-called lock-and-key theory developed by the German chemist Emil Eischer in 1894 (Eigure 13.25). Eischer s hypothesis accounts for the specificity... 

Pharmacophore A pharmacophore is the spatial mutual orientation of atoms or groups of atoms assumed to be recognized by and interact with a receptor or the active site of a receptor. In conjunction with the receptor concept, the notion of a pharmacophore relates directly to the lock-and-key theory proposed by E. Fischer and P. Ehrlich around the beginning of the 20th century (Corpora non agunt nisi fixata). 

Enzymes are basically composed of substrate-binding sites and catalytic sites which are close to each other and cooperatively accelerate the specific reactions. Their substrate specificity is interpreted in terms of the lock and key theory. Various artificial enzymes have been success-... 

The induced-fit theory first described by Daniel E. Koshland. Jr., in 1958 is one of the most fundamental discoveries of our age and is a development of Emil Fischer s well-known lock and key theory,it should be noted that an important characteristic of the key-lock theory is that the enzyme accommodates the substrate without having to change the shape of the active site however, in the induced-fit model, the enzyme changes shape when it reacts, like a glove into which a hand is thrust. To visualize the concepts of induced fit and keylock, two binding models are illustrated in Fig. 1. 

Use the lock-and-key theory to explain specificity in enzyme action. (Section 10.4)... 

An extension of the theory of ES complex formation is used to explain the high specificity of enzyme activity. According to the lock-and-key theory, enzyme surfaces will accommodate only those substrates having specific shapes and sizes. Thus, only specific substrates fit a given enzyme and can form complexes with it (see I Figure 10.4A). 

A limitation of the lock-and-key theory is the implication that enzyme conformations are fixed or rigid. However, research results suggest that the active sites of some enzymes are not rigid. This is taken into account in a modification of the lock-and-key theory known as the induced-fit theory, which proposes that enzymes have somewhat flexible conformations that may adapt to incoming substrates. The active site has a shape that becomes com-planentary to that of the substrate only after the substrate is bound (see I Figure 10.4B). 

The behavior of enzymes is explained by a theory in which the formation of an enzyme-substrate complex is assumed to occur. The specificity of enzymes is explained by the lock-and-key theory and the induced-fit theory. 

Compare the lock-and-key theory with the induced-fit theory. 

An enzyme can catalyze reactions involving propanoic acid, butanoic acid, and pentanoic acid. Would the lock-and-key theory or the induced-fit theory best explain this enzyme s mechanism of action Why ... 

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