How an enzyme surmounts the activation energy barrier

Schowen, Richard L.

doi:10.1073/pnas.2235806100

Cited by 36 publications

(12 citation statements)

References 16 publications

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“…Many enzymes only show specificity for one substrate, while several structurally related substrates can be affected by another type of enzyme [2]. To initiate an enzyme-catalyzed reaction, the enzyme must bind to its substrate forming an enzyme–substrate complex [3]. Considering that the enzymes remain unchanged after the reactions, they catalyze and can be reused.…”

Section: Introductionmentioning

confidence: 99%

Application of the Enzymatic Electrochemical Biosensors for Monitoring Non-Competitive Inhibition of Enzyme Activity by Heavy Metals

Ashrafi

Sýs

Sedláčková

et al. 2019

Sensors

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The inhibition effect of the selected heavy metals (Ag+, Cd2+, Cu2+, and Hg2+) on glucose oxidase (GOx) enzyme from Aspergillus niger (EC 1.1.3.4.) was studied using a new amperometric biosensor with an electrochemical transducer based on a glassy carbon electrode (GCE) covered with a thin layer of multi-wall carbon nanotubes (MWCNTs) incorporated with ruthenium(IV) oxide as a redox mediator. Direct adsorption of multi-wall carbon nanotubes (MWCNTs) and subsequent covering with Nafion® layer was used for immobilization of GOx. The analytical figures of merit of the developed glucose (Glc) biosensor are sufficient for determination of Glc in body fluids in clinical analysis. From all tested heavy metals, mercury(II) has the highest inhibition effect. However, it is necessary to remember that cadmium and silver ions also significantly inhibit the catalytic activity of GOx. Therefore, the development of GOx biosensors for selective indirect determination of each heavy metal still represents a challenge in the field of bioelectroanalysis. It can be concluded that amperometric biosensors, differing in the utilized enzyme, could find their application in the toxicity studies of various poisons.

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Section: Introductionmentioning

confidence: 99%

Application of the Enzymatic Electrochemical Biosensors for Monitoring Non-Competitive Inhibition of Enzyme Activity by Heavy Metals

Ashrafi

Sýs

Sedláčková

et al. 2019

Sensors

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“…He asserted that “the entire and sole source of catalytic power is stabilisation of the TS” [ 6 ], which implied not only that reactant-state binding interactions were by nature inhibitory and only wasted catalytic power ( Fig. 1 ), but also that the particularities of any events occurring along paths between reactants and TS (termed as the “microhistory” of the reaction [ 7 ]) are irrelevant to the catalysis itself. Theories within the “canon” of enzyme catalysis tend to omit or at least de-emphasise the TS, focussing instead on some sort of reactive complex en route from reactants to TS.…”

Section: Discussionmentioning

confidence: 99%

Catalysis: transition-state molecular recognition?

Williams

2010

Beilstein J. Org. Chem.

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SummaryThe key to understanding the fundamental processes of catalysis is the transition state (TS): indeed, catalysis is a transition-state molecular recognition event. Practical objectives, such as the design of TS analogues as potential drugs, or the design of synthetic catalysts (including catalytic antibodies), require prior knowledge of the TS structure to be mimicked. Examples, both old and new, of computational modelling studies are discussed, which illustrate this fundamental concept. It is shown that reactant binding is intrinsically inhibitory, and that attempts to design catalysts that focus simply upon attractive interactions in a binding site may fail. Free-energy changes along the reaction coordinate for SN2 methyl transfer catalysed by the enzyme catechol-O-methyl transferase are described and compared with those for a model reaction in water, as computed by hybrid quantum-mechanical/molecular-mechanical molecular dynamics simulations. The case is discussed of molecular recognition in a xylanase enzyme that stabilises its sugar substrate in a (normally unfavourable) boat conformation and in which a single-atom mutation affects the free-energy of activation dramatically.

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“…From an experimental perspective it may seem pointless to consider such a ‘micro-history’[ 28 , 63 ] of the reaction coordinate, since the only observables are K M and k cat , but it is a useful computational tool to characterize the enzyme. And, as will be argued below, to design better ones.…”

Section: The Underlying Theorymentioning

confidence: 99%

Computational Enzyme Design: Advances, Hurdles and Possible Ways Forward

Linder

2012

Computational and Structural Biotechnology Journal

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This mini review addresses recent developments in computational enzyme design. Successful protocols as well as known issues and limitations are discussed from an energetic perspective. It will be argued that improved results can be obtained by including a dynamic treatment in the design protocol. Finally, a molecular dynamics-based approach for evaluating and refining computational designs is presented.

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How an enzyme surmounts the activation energy barrier

Cited by 36 publications

References 16 publications

Application of the Enzymatic Electrochemical Biosensors for Monitoring Non-Competitive Inhibition of Enzyme Activity by Heavy Metals

Application of the Enzymatic Electrochemical Biosensors for Monitoring Non-Competitive Inhibition of Enzyme Activity by Heavy Metals

Catalysis: transition-state molecular recognition?

Computational Enzyme Design: Advances, Hurdles and Possible Ways Forward

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