Intramolecular Models Depicting the Kinetic Importance of „fit” in Enzymatic Catalysis

Bruice, Thomas C.; Pandit, U. K.

doi:10.1073/pnas.46.4.402

Cited by 107 publications

(66 citation statements)

References 2 publications

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“…Entropy lost by immobilizing a substrate on the bind ing site, in an orientation suitable for reaction (relative to the state in which enzyme and substrate are solvated) , has the effect of reducing the ac tivation energy. Similar constraint of a small molecule has been shown to increase a reaction rate by 5 X 104 (75). The ratio of deacylation rates of N-acetyltryptophanyl chymotrypsin compared to its glycyl analogue is 560 (76).…”

Section: Enzyme Catalysismentioning

confidence: 83%

X-Ray Diffraction Studies of Enzymes

Blow¹,

Steitz²

1970

Annu. Rev. Biochem.

201

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Section: Enzyme Catalysismentioning

confidence: 83%

X-Ray Diffraction Studies of Enzymes

Blow¹,

Steitz²

1970

Annu. Rev. Biochem.

201

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“…When the rate-limiting step of a reaction in aqueous solution involves the attack at a hydrophobic group by a charged and hence strongly hydrated nucleophile, the activation energy also includes the free energy needed for partially dehydrating the nucleophile.2'3 In such cases the observed proximity effect can be several orders of magnitude larger than that computed from the change in translational entropy of the reacting groups. 4 According to the strain theory,5 when a substrate is bound at the active site in the enzyme-substrate complex, the susceptible bond is already distorted or under strain so that it is rendered more reactive. Observations on lysozyme6 and a model catalyst7 seem to support this possibility.…”

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confidence: 99%

Directional Character of Proton Transfer in Enzyme Catalysis

Wang¹

1970

Proc. Natl. Acad. Sci. U.S.A.

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Abstract. Hydrogen bonding can facilitate proton transfer in certain direqtions and retard proton transfer in certain other directions. By assuming that directed proton transfer along strategically oriented hydrogen bonds in the enzyme-substrate complex plays an important role in determining the efficiency and specificity of the enzyme, we present a unified interpretation for the reported observations on carbonic anhydrase and a-chymotrypsin.Introduction. It is generally agreed that enzyme catalysis owes its efficiency and specificity to the way in which the enzyme and its substrate fit each other. But how do we define fitness in precise terms and explain the enhancement ill reaction rate? Here the opinions differ.According to the proximity theory,1 the main advantage of enzyme catalysis is that the reacting groups are already held together in the enzyme-substrate complex and consequently the activation step does not involve as large an entropy decrease as in most nonenzymatic reactions. When the rate-limiting step of a reaction in aqueous solution involves the attack at a hydrophobic group by a

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“…It is our contention that if orbital steering has any physical significance, the experi- kcal/mol or more) and this, coupled with a consecutive increase in ASi toward zero for the series, could easily lead to an observed ,AFt of about 3 kcal/mol (12,13). One might note that the model depicted by Table 1 bears a striking resemblance to one offered in 1960, whichwas atthattimeinterpreted to indicate "the tremendous enhancement in rate that an enzyme could achieve by fixing the reacting species in a steric conformation closely resembling that of the transition state for the reaction " (14).…”

Section: Discussionmentioning

confidence: 98%

On the Concept of Orbital Steering in Catalytic Reactions

Bruice

Brown²,

Harris³

1971

Proc. Natl. Acad. Sci. U.S.A.

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Angular displacement from linear overlap of but a few degrees in the transition state of the enzymesubstrate complex has been postulated to be of great kinetic significance ("orbital steering"). The concept of orbital steering is shown to have evolved from the orientation parameters of an equation previously proposed to evaluate the kinetic importance of propinquity. This equation is shown to be naive. Arguments provided against the concept of orbital steering include: (a) force constants predicted from orbital steering are about 100 times those experimentally determined from displacement of nuclei in a direction normal to the axis of a covalent bond (for example, at room temperature vibrational bending amplitudes of +50 or more are common); (b) because of the lessened directionality of orbitals containing nonbonded electron pairs, the force constants in transition states should be even smaller than in the case of a covalent bond; and (c) molecular orbital calculations predict shallow total energy minima for orbital alignment. The experimental rate data offered as a basis for the concept of orbital steering are shown to find rationalization in the previously observed dependence of ASt on kinetic order and the energy requirements for the freezing-out of single bonds in the transition state leading to the formation of medium-size ring compounds from extended ground states. It is concluded that if orbital steering does exist, experimental and theoretical evidence to support this concept have yet to be presented.A task of the physical organic chemist has been one of providing useful models for enzymatic processes. Any proposed model must be consistent with what we know to be true in terms of the fundamental theories and principles of basic physics and chemistry. In this paper we shall present a discussion of the implications of a recently proposed model, termed orbital steering (1), whose purpose is to explain the large enhancement of the rates of a particular set of intramolecular reactions over their intermolecular counterparts. We will in addition present an alternative interpretation of the experimental observations in question, based on thermodynamics and reaction rate theory. DISCUSSIONThe contribution of the proper approximation of reacting groups in the productive enzyme-substrate complex to the efficiency of enzyme catalysis has been widely discussed. A very popular treatment (2)

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Intramolecular Models Depicting the Kinetic Importance of „fit” in Enzymatic Catalysis

Cited by 107 publications

References 2 publications

X-Ray Diffraction Studies of Enzymes

X-Ray Diffraction Studies of Enzymes

Directional Character of Proton Transfer in Enzyme Catalysis

On the Concept of Orbital Steering in Catalytic Reactions

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