Lock and key theory

6 Key excerpts on "Lock and key theory"

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  Enzymes

  A Practical Introduction to Structure, Mechanism, and Data Analysis

  • Robert A. Copeland(Author)
  • 2004(Publication Date)
  • Wiley-Interscience

    (Publisher)

  In the late nineteenth century Emil Fisher formulated these concepts into the lock and key model, as illustrated in Figure 6.2. In this model the enzyme active site and the substrate molecule are viewed as static structures that are stereochemically complementary. The insertion of the substrate into the static enzyme active site is analogous to a key fitting into a lock, or a jigsaw piece fitting into the rest of the puzzle: the best fits occur with the substrates that best complement the structure of the active site; hence these molecules bind most tightly. Active site—substrate complementarity results from more than just stereochemical fitting of the substrate into the active site. The two structures must also be electrostatically complementary, ensuring that charges are 148 CHEMICAL MECHANISMS IN ENZYME CATALYSIS Figure 6.2 Schematic illustration of the lock and key model of enzyme— substrate interactions. counterbalanced to avoid repulsive effects. Likewise, the two structures must complement each other in the arrangement of hydrophobic and hydrogen- bonding interactions to best enhance binding interactions. Enzyme catalysis is usually stereo-, regio-, and enantiomerically selective. Hence substrate recognition must result from a minimum of three contact points of attachment between the enzyme and the substrate molecule. Consider the example of the alcohol dehydrogenases (Walsh, 1979) that catalyze the transfer of a methylene hydrogen of ethyl alcohol to the carbon at the 4-position of the NAD cofactor, forming NADH and acetaldehyde. Studies in which the methylene hydrogens of ethanol were replaced by deuterium demonstrated that alcohol dehydrogenases exclusively transferred the pro-R hydrogen to NAD (Loewus et al., 1953; Fersht, 1985).

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  The Construction of Analogy-Based Research Programs

  The Lock-and-Key Analogy in 20th Century Biochemistry

  • Rebecca Mertens(Author)
  • 2019(Publication Date)
  • transcript Verlag

    (Publisher)

  43 Yet I also argue that concentrating on this repressive role of the analogy reveals just one aspect of its history in biochemistry. In some contexts, this reductionist view left an open space for conceptual exploration and allowed cooperation between chemists and biologists. Focusing on cases of lock-and-key analogy usage in the fields of enzymology (chapter 2), immunology (chapter 3), and mo-lecular biology (chapter 4) in the first half of the 20 th century, the present study shows that the analogy also served as an instrument for the inclusion of different biochemical fields. Furthermore, it sheds light on the conditions for the analogy becoming so successful such as to suppress other concepts and models in other biochemical and biomedical contexts in the 20 th centu-ry. 39 Ibid., p. 169. 40 Martin (1991): The egg and the sperm, p. 496. 41 Ibid., pp. 496ff. 42 Ibid. 43 This becomes especially clear in the context of Linus Pauling’s usage of the lock-and-key analogy for the extension of his claims on stereocomplementarity to ge-netics, embryology and immunochemistry (See the present study, chapter 4). 1. Influence of the lock-and-key analogy on 20 th century biochemistry | 21 In sum, although it is commonly assumed that the lock-and-key analogy had a huge influence on biochemical thought and education in the 20 th cen-tury, it has not been specified yet how this influence is to be characterized. This is in part due to the lack of a long-term analysis of the analogy in its various scientific contexts. From a historical perspective, the present study can be seen as a contribution to such a long-term analysis. It concentrates on the role of the lock-and-key analogy in the making of research programs and reveals new aspects of the mutual interactions between analogy usage, model making and the organization of research in terms of epistemic, so-cial, and political activities.

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  The Lock-and-Key Principle

  The State of the Art--100 Years On

  • Jean-Paul Behr(Author)
  • 2008(Publication Date)
  • Wiley

    (Publisher)

  Waser, (formerly California Institute of Technology) 6120 Terryhill Drive, La Jolla, CA 92037, USA vii PREFACE In 1894, a farsighted (bio)chemist came up with an idea that would provide the key to understanding the phenomena of molecular recognition that underlie life itself. After a century of refinement his concept still remains productive, as is evident from the many scientists who draw on it. This book is their tribute to the man who unlocked our thought. ix Chapter 1 Emil Fischer’s Lock-and-Key Hypothesis after 100 years- Towards a Supracellular Chemistry FRIEDRICH CRA MER Max-Planck-Institutfur Experimentelle Medizin, Gottingen, Germany 1. INTRODUCTION Around 100 years ago Emil Fischer in his famous paper [ 1 ] proposed that enzyme and substrate can be compared to lock and key. Since that time this metaphor has been used to describe enzyme action. In this chapter we shall try to explore whether this metaphor still holds. On the one hand, enzymology has made enormous progress in these 100 years, but on the other hand the lock- and-key concept has greatly changed. In Figure 1 three types of ‘keys’ are shown. The classical key, which Emil Fischer had in mind, is pushed into the lock and turned clockwise in order to open the lock. Thus, the process is chiral. The key shown in the figure was manufactured in the year 1853, one year after Emil Fischer was born; thus, probably this type of key was imprinted in the young boy’s conceptual memory. Today, the keys have become much more refined. Around the turn of the century the safety lock was invented, which does a kind of proof- reading of the key. At present an entirely new system is being installed; namely the magnetic card. This card can unlock money sources and hotel rooms. We shall discuss further these three key concepts and give a few examples of each of them. 2. CLASSICAL LOCKS One almost classical molecule for lock-and-key studies is cyclodextrin.

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  Introduction to Peptides and Proteins

  • Ulo Langel, Benjamin F. Cravatt, Astrid Graslund, N.G.H. von Heijne, Matjaz Zorko, Tiit Land, Sherry Niessen(Authors)
  • 2009(Publication Date)
  • CRC Press

    (Publisher)

  Additionally, enzymes not only constitute the key points of metabolic regula-tion but are also very important in biotechnology for producing a variety of biomolecules and drug precursors, and in medicine for diagnostics and therapy. The idea of producing an enzyme with designed specificity and activity led to their construction based on antibodies. These “artificial” enzymes are called abzymes or catalytic antibodies, and are discussed in Chapter 30. Besides pro-teins, some RNA molecules also have catalytic properties. Catalytic RNAs are called ribozymes and have an important role in the maturation of certain RNA molecules and in protein synthesis, as discussed in Chapter 16. 21.1 ACTIVE SITE CONCEPT The active site, the region where an enzyme binds its substrate, is only a small part of the enzyme molecule. It recognizes the substrate molecule, in whole or in part, by establishing several usually weak bonds with appropriately oriented functional groups of the amino acid residues within the active site. Binding energy is the only energy available to the enzyme for converting substrate into the product along an alternative reaction pathway that is faster than that in the absence of enzyme. How this is done is the subject of the catalytic mechanism and will be discussed later in this chapter. Recognition of substrate by enzyme was for a long time regarded as static. In 1890, Fischer postulated the lock-and-key principle in which enzyme active site was compared to the lock and substrate to the key that precisely fitted the lock without any changes in the enzyme structure. Koshland, in 1958, put forward the opposing theory of “induced fit,” in which the enzyme adapts to the substrate by con-formational changes in the active site (see Chapter 17, Figure 17.2).

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  Introduction to Proteins

  Structure, Function, and Motion, Second Edition

  • Amit Kessel, Nir Ben-Tal(Authors)
  • 2018(Publication Date)
  • Chapman and Hall/CRC

    (Publisher)

  ] .

  As explained in the introduction to this chapter, chemical reactions proceed from reactant(s) to product(s) through a sequence of intermediates, which differ from one another in their chemistry, configuration, and free energy. Like other catalysts, enzymes accelerate chemical reactions by lowering the energy barrier associated with the transition state — a reaction intermediate with the highest free energy. However, in contrast to other simple catalysts like metals, most enzymes are highly specific to the types of reactions they accelerate, and to the substrates on which they act. This specificity is achieved thanks to the ‘active site ’, a pocket-like depression in the structure of the enzyme, to which the substrate binds and in which the chemical reaction is accelerated. The active site fulfils two major functions

  [145 ]

  :

  1. Substrate bindingthe active sites of enzymes may bind a variety of substrates, including small molecules (e.g., monosaccharides or amino acids), moderate-size molecules (e.g., short peptides) and even macromolecules (e.g., proteins and polysaccharides) [
     145
     ] . Accordingly, active sites may vary greatly in size, with sizes typically ranging between 400
     A

     o 2
     and 2,000
     A

     o 2
     [146 ]
     . Substrate binding is mediated through multiple noncovalent interactions between different parts of the substrate and chemical groups in the active site (Figure 9.22). These interactions render the binding specific, which accounts for the selectivity of enzymes to their natural (cognate) substrates (see below). The binding interactions also provide the energy used for keeping the substrate inside the active site, which accounts for the affinity between the two. The interactions mainly involve active site amino acids. Indeed, the side chains of binding residues offer a diverse set of chemical groups: nonpolar (linear or branched), hydroxyl, thiol, amine, amide, carboxylate, imidazole, indole, phenol, and guanidinium
     [147 ]
     (Figure 9.23; see also Figure 2.5 and Table 2.1 in Chapter 2 ). Some active sites interact with their substrates via additional chemical groups, which may be components of small organic molecules (e.g., nucleotides, small carbohydrate units, and lipids), metals, or other inorganic species (e.g., water) (see Section 9.3 below). As explained in Chapters 2 and 8 , these molecular adducts, which in enzymes are usually referred to as ‘cofactors ’, may be permanently attached ‘prosthetic groups ’ or transiently bound ‘coenzymes ’
     [148

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  Textbook of Structural Biology

  • Anders Liljas, Lars Liljas;Miriam-Rose Ash;G?ran Lindblom;Poul Nissen;Morten Kjeldgaard(Authors)
  • 2016(Publication Date)
  • WSPC

    (Publisher)

  8

  Enzymes

  Enzymes are proteins that catalyze biochemical reactions without being consumed, and are able to perform the same reaction over and over again. They have a wide range of catalytic properties and are classified on that basis (hydrolases, ligases, reductases, oxidases and so on).

  Enzymes are usually large molecules, but only a small fraction of the amino acid residues participate in the catalysis. The area of an enzyme where the binding of the substrate(s) and the catalysis occurs is called the active site. The active sites are frequently located in some sort of depression or cavity in the structure of the enzyme. Sometimes cofactors (like metal ions) or coenzymes (like NADH) are bound in the active site and participate in the reaction.

  Many enzymes are highly specific for their substrates. This is generated by complementarities in shape of the substrate and the active site. The complementarity may also include the charge, polarity and hydrophobicity relationship between substrate and active site. Due to this complementarity enzymes are often highly stereospecific, substrates with the wrong hand may not be able to bind. Different models have been used to describe the interaction between enzyme and substrate. An early description is the “lock and key model” which illustrates the complementarity but not how the enzyme may function.

  Enzymes are flexible molecules like all proteins. The dynamics involve atomic oscillations, side chain reorientation and movements of main chain or of whole domains. This dynamic character is essential for enzyme activity. During binding and catalysis residues of the active site or large parts of the enzymes can undergo conformational changes just like the substrate going through chemical changes. One model that emphasizes the conformational changes of enzyme as well as substrate is called “induced fit” (Figure 8.1

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