lock and key hypothesis

Lock-and-key model

strong>Lock-and-key model n., [lɑk ænd ki ˈmɑdl̩] Definition: a model for enzyme-substrate interaction

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Lock-and-key model Definition

Lock-and-key model is a model for enzyme-substrate interaction suggesting that the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. In this model, enzymes are depicted as highly specific. They must bind to specific substrates before they catalyze chemical reactions . The term is a pivotal concept in enzymology to elucidate the intricate interaction between enzymes and substrates at the molecular level. In the lock-and-key model, the enzyme-substrate interaction suggests that the enzyme and the substrate possess specific complementary geometric shapes that fit exactly into one another. Like a key  into a  lock , only the correct size and shape of the substrate ( the key ) would fit into the  active site  ( the keyhole ) of the enzyme ( the lock ).

Compare: Induced fit model   See also: enzyme , active site , substrate

Lock-and-key vs. Induced Fit Model

At present, two models attempt to explain enzyme-substrate specificity; one of which is the lock-and-key model , and the other is the Induced fit model . The lock and key model theory was first postulated by  Emil Fischer   in 1894. The lock-and-key enzyme action proposes the high specificity of enzymes. However, it does not explain the stabilization of the transition state that the enzymes achieve. The induced fit model (proposed by Daniel Koshland in 1958) suggests that the active site continues to change until the substrate is completely bound to the active site of the enzyme, at which point the final shape and charge are determined. Unlike the lock-and-key model, the induced fit model shows that enzymes are rather flexible structures. Nevertheless, Fischer’s Lock and Key theory laid an important foundation for subsequent research, such as during the refinement of the enzyme-substrate complex mechanism, as ascribed in the induced fit model. The lock-and-key hypothesis has opened ideas where enzyme action is not merely catalytic but incorporates a rather complex process in how they interact with the correct substrates with precision.

Key Components

Components of the lock and key model:

• Enzyme : the enzyme structure is a three-dimensional protein configuration, with an active site from where the substrate binds.
• Substrate : often an organic molecule, a substrate possesses a structural feature that complements the geometry of the enzyme’s active site.

In the lock and key model, both the enzymes and the substrates facilitate the formation of a complex that lowers the activation energy needed for a chemical transformation to occur. Such reduction in the activation energy allows the chemical reaction to proceed at a relatively faster rate, making enzymes crucial in various biological and molecular processes.

Lock-and-key Model Examples

Some of the common examples that are often discussed in the context of the Lock and Key Model are as follows:

• Enzyme lactate dehydrogenase with a specific active site for its substrates, pyruvate and lactate. The complex facilitates the interconversion of pyruvate and lactate during anaerobic respiration
• Enzyme carbonic anhydrase with a specific active site for the substrates carbon dioxide and water. The complex facilitates the hydration of carbon dioxide, forming bicarbonate
• Enzyme lysozyme binding with a bacterial cell wall peptidoglycan, which is a vital immune function

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• Aryal, S. and Karki, P. (2023).  “Lock and Key Model- Mode of Action of Enzymes”. Microbenotes.com. https://microbenotes.com/lock-and-key-model-mode-of-action-of-enzymes/
• Farhana, A., & Lappin, S. L. (2023, May).  Biochemistry, Lactate Dehydrogenase . Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK557536/

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Last updated on January 11th, 2024

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Microbe Notes

Lock and Key Model- Mode of Action of Enzymes

Enzymes are biological catalysts. These are commonly proteins but also include RNA (ribozymes) molecules that catalyze chemical reactions by lowering the activation energy of a reaction. These are known to speed up the rate of a reaction millions of times faster than the reaction without enzymes. Nearly all biological reactions require enzymes to transform substrate into products. The substrate is the reactant molecule upon which enzymes act during a chemical reaction, and products are the substances formed as a result of a chemical reaction. A single reactant molecule can decompose to give multiple products. Similarly, two reactants can enter into a reaction to yield products. These are reusable even after the completion of the reaction. Chemical properties such as charge and pH are vital in enzymatic reactions.

Binding between enzymes and reactant molecules takes place in such a way that chemical bond-breaking and bond-forming processes occur more readily. Meanwhile, no change in ∆the G value of a reaction takes place, thereby not altering the energy-releasing or energy-absorbing process of the reaction. However, it lowers the energy of the transition state, the topmost unstable state where the activated complex is formed from reactants that later give products.

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Interesting Science Videos

Enzyme’s Active site and Substrate Specificity

Enzymes are relatively larger than the substrates, whose only a small fraction is involved in catalysis by reducing chemical activation energy, also known as the catalytic site, and the other portion for binding with the substrate and orienting them also known as the binding site. The catalytic site and binding site altogether form the active site of an enzyme. Usually, there are two active sites in an enzyme.

•  The active site of enzymes is a cleft portion, composed of a small number of a unique combination of amino acid residues, usually three to four in number, which make up only ~10-20% of the volume of an enzyme. 
• The remaining amino acids are used to maintain tertiary structure by proper scaffold folding through non-covalent interactions.
• Non-covalent interaction between enzyme and substrate in correct orientation favors their reaction. These interactions include hydrogen bonds , hydrophobic bonds, ionic interactions, and Van der Waal’s interactions.
• However, transient covalent bonds between enzymes and substrates are also formed during the time of reaction.
• Side chains of amino acids play an important role in highly specific three-dimensional conformation at the level of the active site. These are large or small, hydrophilic or hydrophobic, acidic or basic.
• The specific shape, size, and chemical behavior of enzymes are determined by the nature of amino acids and their 3D space in the active site.

Specificity is a distinctive feature of enzymes where they have a unique ability to choose an exact substrate from a group of similar chemical molecules. Their specificity towards their substrate varies to a different extent. These are of different types, namely: Bond specificity, Group specificity. Substrate specificity, Stereospecificity, Geometrical specificity, and Co-factor specificity.

Substrate specificity is also k/a absolute specificity for the enzyme’s specificity towards one substrate and one reaction. For e.g., Lactase acts on the B-1-4 glycosidic linkage of lactose to yield galactose and glucose. The restrictive nature of enzymes towards the choice of substrate can be attributed to the enzymatic activity of two oxidoreductase enzymes. Alcohol dehydrogenase uses its substrate alcohol while lactic acid dehydrogenase act on lactic acid. Although these two enzymes function with the mechanism of oxidation and reduction reaction, their substrates can’t be used interchangeably. This is because the different structure of each substrate prevents their fitting into the active site of the alternative enzyme.

In most cases, cofactors, the non-protein molecules, are required to ensure an efficient enzyme-facilitated chemical reaction. These function to bind with enzymes via either ionic interaction or covalent interactions. Metal ions (such as minerals) and co-enzymes (vitamin derivatives) are cofactors.

Lock and Key Model

A German scientist, Emil Fischer postulated the lock and key model in 1894 to explain the enzyme’s mode of action. Fischer’s theory hypothesized that enzymes exhibit a high degree of specificity towards the substrate. This model assumes that the active site of the enzyme and the substrate fit perfectly into one another such that each possesses specific predetermined complementary geometric shapes and sizes. Thus, the shape of the enzyme and substrate do not influence each other. This specificity is analog to the lock and key model, where the lock is the enzyme, and the key is the substrate. In certain circumstances, if a second substrate similar in shape and size to the primary substrate is made to bind to the enzyme, this second substrate also fits in the active site too.

How does Lock and Key Model work?

• Binding of the substrate(s) to the enzyme at their active site takes place, thereby forming an enzyme-substrate complex.
• Enzymes catalyze the chemical reaction to take place, which can either be a synthesis reaction (favors bond formation) or a decomposition reaction (favors bond breakage).
• As a result, the formation of one or more products takes place, and the enzymes are released for their reuse in the next reaction.

Limitations of Lock and Key Model

• It doesn’t explain how the enzyme-substrate complex is stabilized in the transition state.
• This model supposes the enzyme is a rigid structure whose shape does not change upon binding with a suitable substrate. However, this is not supported by recent research, which states that there is a change in conformation of the active site of the enzyme upon binding of substrate.
• It does not describe the condition for binding multiple substrates to the enzyme.

Later, it was found that enzyme specificity toward one substrate is not always true. Although there are enzymes that specifically bind with only one substrate, there are also enzymes that exhibit broad specificity towards different but similarly structured substrates, such as lipase that can bind to different types of lipids. Similarly, proteases such as trypsin and chymotrypsin can degrade multiple types of proteins. Thus, the lock and key model is flawed, and the induced fit model was introduced to give a more refined view of the mode of enzymatic action.

• Blanco, A., & Blanco, G. (2017). Medical Biochemistry. Academic Press. https://www.khanacademy.org/science/ap-biology/cellular-energetics/enzyme-structure-and-catalysis/a/enzymes-and-the-active-site
• https://www.biologyonline.com/dictionary/substrate-specificity
• https://www.britannica.com/science/protein/The-mechanism-of-enzymatic-action
• https://www.biologyonline.com/dictionary/lock-and-key-model
• https://study.com/learn/lesson/lock-key-model-vs-induced-fit-model.html
• https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_(McMurry)/26%3A_Biomolecules-_Amino_Acids_Peptides_and_Proteins/26.11%3A_Enzymes_and_Coenzymes
• https://en.wikibooks.org/wiki/Structural_Biochemistry/Protein_function/Lock_and_Key
• https://ib.bioninja.com.au/higher-level/topic-8-metabolism-cell/untitled-6/models-of-action.html

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Molecular Recognition: Lock-and-Key, Induced Fit, and Conformational Selection

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• Todd Holyoak 2  

Fluctuation fit ; Population selection ; Population shift ; Preexisting equilibrium ; Selected fit

In the most general sense, molecular recognition corresponds to the mechanism by which two or more molecules come together to form a specific complex. These types of specific molecular interactions span biology and include processes as diverse as enzyme catalysis, antibody–antigen recognition, protein synthesis, and transcriptional regulation to name but a few. As a consequence of the universal importance of molecular recognition in biological function, understanding how molecules specifically recognize and interact with one another is of fundamental importance.

Introduction

Early studies on the kinetics and specificity of enzyme-catalyzed reactions led to the conclusion that substrates combine with the enzyme at a specific active site location on the enzyme surface. This understanding generated new questions as to how enzymes could carry out chemical transformations...

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Holyoak, T. (2013). Molecular Recognition: Lock-and-Key, Induced Fit, and Conformational Selection. In: Roberts, G.C.K. (eds) Encyclopedia of Biophysics. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-16712-6_468

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The Lock and Key Theory: Understanding Enzyme Specificity and Catalysis

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The Lock and Key Theory, introduced by Emil Fischer, is a fundamental concept in biochemistry that explains enzyme specificity. It compares the enzyme's active site to a lock and the substrate to a key, illustrating how only the correct substrate can initiate a reaction. This theory is pivotal in understanding biochemical pathways, organic chemistry, and pharmaceuticals, influencing drug design by targeting enzyme active sites to treat diseases.

The Fundamentals of Enzyme Specificity: Lock and Key Theory

Exploring the Components and Dynamics of the Lock and Key Model

The role of the lock and key theory in organic chemistry and drug discovery, lock and key versus induced fit: diverse models of enzyme specificity, educational resources for grasping the lock and key theory, the enduring influence of the lock and key theory on biochemical science.

Mostra di più

Introduction to the Lock and Key Theory

Definition of the lock and key theory.

The Lock and Key Theory explains the specificity of enzyme action by comparing the enzyme's active site to a lock and the substrate to a key

Elements of the Lock and Key Theory

Enzyme and its active site

Enzymes are specialized proteins with a three-dimensional pocket, called the active site, designed to bind specific substrates

Substrates are molecules that bind to the enzyme's active site, triggering a specific reaction

Enzyme-substrate complex and product

The binding of the substrate to the active site forms an enzyme-substrate complex, which facilitates the conversion of the substrate into the product

Reaction sequence in the Lock and Key Theory

The Lock and Key Theory can be summarized by the reaction sequence \(E + S \rightarrow ES \rightarrow E + P\), where \(E\) represents the enzyme, \(S\) the substrate, \(ES\) the enzyme-substrate complex, and \(P\) the product

Applications of the Lock and Key Theory

Importance in biochemistry and pharmaceutical industry.

The Lock and Key Theory is a fundamental concept in biochemistry and is crucial in drug design for developing specific and effective pharmaceutical agents

Comparison with the Induced Fit Theory

The Induced Fit Theory complements the Lock and Key model by suggesting that the active site is dynamic and can adapt to accommodate slight variations in substrate structure

Educational resources for learning the Lock and Key Theory

Detailed diagrams and glossaries are valuable tools for understanding the step-by-step process of enzyme action and the key terms associated with the Lock and Key Theory

Significance of the Lock and Key Theory

Influence on our understanding of enzymatic function.

The Lock and Key Theory has greatly contributed to our understanding of enzymatic function and the complex chemical processes that sustain life

Practical applications in drug design

The Lock and Key Theory is essential in the development of enzyme inhibitors for treating diseases by disrupting pathological processes

Role in biochemistry education and research

The Lock and Key Theory remains a fundamental concept in biochemistry education and research, providing a starting point for exploring the complexities of enzyme behavior

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Enzymes, which are specialized ______, work as catalysts and their action is explained by the ______ and Key Theory.

proteins Lock

Describe the active site of an enzyme.

Three-dimensional pocket on enzyme surface; binds substrate with high specificity; involves non-covalent interactions like hydrogen bonds, ionic interactions, van der Waals forces.

Explain the enzyme-substrate complex.

Transient complex formed when substrate binds to enzyme's active site; facilitates substrate's conversion into product.

Summarize the reaction sequence in the Lock and Key Theory.

E + S -> ES -> E + P; E is enzyme, S is substrate, ES is enzyme-substrate complex, P is product; enzyme remains unchanged post-reaction.

The ______ and Key Theory is crucial for understanding enzyme catalysis in organic chemistry and drug design in the pharmaceutical industry.

Originator of Induced Fit Theory

Daniel Koshland proposed the Induced Fit Theory in 1958.

Characteristic of enzyme's active site in Induced Fit Theory

Active site is dynamic, molds around substrate upon binding.

Role of substrate structure variability in enzyme specificity

Enzyme adaptability allows accommodation of substrates with slight structural variations.

Educational materials like ______ and glossaries are crucial for grasping the ______ Theory.

detailed diagrams Lock and Key

Lock and Key Theory - Basic Concept

Theory where enzymes and substrates fit together precisely like a lock and key, explaining enzyme specificity.

Enzyme Specificity - Importance

Critical for enzymes to catalyze only the correct reactions, ensuring proper metabolic function.

Drug Design - Lock and Key Relevance

Lock and Key Theory guides creation of enzyme inhibitors that mimic substrates, blocking unwanted reactions in disease.

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Structural Biochemistry/Protein function/Lock and Key

In the Lock and Key Model, first presented by Emil Fisher, the lock represents an enzyme and the key represents a substrate. It is assumed that both the enzyme and substrate have fixed conformations that lead to an easy fit. Because the enzyme and the substrate are at a close distance with weak attraction, the substrate must need a matching shape and fit to join together. At the active sites, the enzyme has a specific geometric shape and orientation that a complementary substrate fits into perfectly. The theory behind the Lock and Key model involves the complementarity between the shapes of the enzyme and the substrate. Their complementary shapes make them fit perfectly into each other like a lock and a key. According to this theory, the enzyme and substrate shape do not influence each other because they are already in a predetermined perfectly complementary shape. As a result, the substrate will be stabilized. This theory was replaced by the induced fit model which takes into account the flexibility of enzymes and the influence the substrate has on the shape of the enzyme in order to form a good fit.

The active site is the binding site for catalytic and inhibition reaction of the enzyme and the substrate; structure of active site and its chemical characteristic are of specificity for binding of substrate and enzyme. Three models of enzyme-substrate binding are the lock-and-key model, the induced fit model, and the transition-state model. The lock-and-key model assumes that active site of enzyme is good fit for substrate that does not require change of structure of enzyme after enzyme binds substrate.

• Book:Structural Biochemistry

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