Tunneling and Dynamics in Enzymatic Hydride Transfer

Nagel, Zachary D.; Klinman, Judith P.

doi:10.1021/cr050301x

Cited by 311 publications

(348 citation statements)

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“…excitonic transport in photosynthetic pigments, coherent spin dynamics in avian magnetoreception, inelastic electron tunneling in olfaction, and hydrogen tunneling in enzyme catalysis [1][2][3][4][5][6][7][8][9][10][11]. This is not only intriguing from a physics perspective -given the noisy high-temperature ambience in these situations -but also promises to reveal robust ways to harness 'quantumness' for engineering new and improved systems, both biomimetic and otherwise.…”

Section: Introductionmentioning

confidence: 99%

State transitions and decoherence in the avian compass

Poonia

Saha

2015

Phys. Rev. E

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The radical pair model has been successful in explaining behavioral characteristics of the geomagnetic compass believed to underlie the navigation capability of certain avian species. In this study, the spin dynamics of the radical pair model and decoherence therein are interpreted from a microscopic state transition point of view. This helps to elucidate the interplay between the hyperfine and Zeeman interactions that enables the avian compass, and the distinctive effects of nuclear and environmental decoherence on it. Using a quantum information theoretic quantifier of coherence, we find that nuclear decoherence induces new structure in the spin dynamics without materially affecting the compass action; environmental decoherence, on the other hand, completely disrupts it.

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Section: Introductionmentioning

confidence: 99%

State transitions and decoherence in the avian compass

Poonia

Saha

2015

Phys. Rev. E

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“…Tunneling mechanisms have been shown in a wide array of cofactor-dependent enzymes, including flavoenzymes. Examples of flavoenzymes in which the tunneling mechanisms have been demonstrated include morphinone reductase (29,30), pentaerythritol tetranitrate reductase (29), glucose oxidase (31)(32)(33), and choline oxidase (34). Mechanistic data on Class 2 dihydroorotate dehydrogenases, also with a flavin cofactor (FMN) covalently linked to the protein moiety (35,36), could only propose a mechanism that is either stepwise or concerted with significant quantum mechanical tunneling for the hydride transfer from C6 and the deprotonation at C5 in the oxidation of dihydroorotate to orotate (37).…”

mentioning

confidence: 99%

Contribution of Flavin Covalent Linkage with Histidine 99 to the Reaction Catalyzed by Choline Oxidase

Quaye¹,

Cowins

Gadda

2009

Journal of Biological Chemistry

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A number of enzymes, including dehydrogenases (1-3), monooxygenases (4 -7), halogenases (8 -11), and oxidases (7, 12, 13), employ flavin cofactors (FAD or FMN) for their catalytic processes. About a tenth of all flavoproteins have been shown to contain a covalently attached cofactor, which may be linked at the C8M position via histidyl, tyrosyl, or cysteinyl side chains or at the C6M position via a cysteinyl side chain (14). Glucooligosaccharide oxidase (15, 16), hexose oxidase (17), and berberine bridge enzyme (18,19) The discovery of quantum mechanical tunneling in enzymatic reactions, in which hydrogen atoms, protons, and hydride ions are transferred, has attracted considerable interest in enzyme studies geared toward understanding the mechanisms underlying the several orders of magnitudes in the rate enhancements of protein-catalyzed reactions compared with non-enzymatic ones. Tunneling mechanisms have been shown in a wide array of cofactor-dependent enzymes, including flavoenzymes. Examples of flavoenzymes in which the tunneling mechanisms have been demonstrated include morphinone reductase (29, 30), pentaerythritol tetranitrate reductase (29), glucose oxidase (31-33), and choline oxidase (34). Mechanistic data on Class 2 dihydroorotate dehydrogenases, also with a flavin cofactor (FMN) covalently linked to the protein moiety (35,36), could only propose a mechanism that is either stepwise or concerted with significant quantum mechanical tunneling for the hydride transfer from C6 and the deprotonation at C5 in the oxidation of dihydroorotate to orotate (37). This leaves choline oxidase as the only characterized enzyme with a covalently attached flavin cofactor (12,38), where the oxidation of its substrate occurs unequivocally by quantum mechanical tunneling.Choline oxidase from Arthrobacter globiformis catalyzes the two-step FAD-dependent oxidation of the primary alcohol substrate choline to glycine betaine with betaine aldehyde, which is predominantly bound to the enzyme and forms a gem-diol species, as intermediate (Scheme 1). Glycine betaine accumulates in the cytoplasm of plants and bacteria as a defensive mechanism against stress conditions, thus making genetic engineering of relevant plants of economic interest (39 -45), and the biosynthetic pathway for the osmolyte is a potential drug target in human microbial infections of clinical interest (46 -48). The first oxidation step catalyzed by choline oxidase involves the transfer of a hydride ion from a deprotonated choline to the protein-bound flavin followed by reaction of the anionic flavin hydroquinone with molecular oxygen to regenerate the oxidized FAD (for a recent review see Ref. 50). The gem-diol choline, i.e. hydrated betaine aldehyde, is the substrate for the second oxidation step (49), suggesting that the reaction may follow a similar mechanism. The isoalloxazine ring of the flavin cofac-

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“…Se a amostragem conformacional é feita corretamente durante as simulações computacionais, estes efeitos, chamados de reorganização da estrutura enzimática 23 , são incorporados normalmente 18,21,24 e não representam um mecanismo catalítico em particular 8,41 . A liberdade conformacional não deve ser confundida com as flutuações dinâmicas da estrutura protéica, principalmente as vibrações que amplificam efeitos quânticos como tunelamento 47,48 . A teoria generalizada do estado de transição 3,49 pode ser usada para racionalizar estes efeitos.…”

Section: Efeitos Quânticos E Dinâmicosunclassified

“…Contribuições de até 3 ordens de magnitude para o aumento da velocidade de reações enzimáticas foram atribuídas à dinâmica da proteína, ou seja, às vibrações que amplificam o tunelamento em comparação com a reação em solução, nos sistemas em que uma transferência de hidrogênio (tanto nas formas H + , H neutro e H -) é determinante da velocidade de reação 8,43,50 . As desidrogenases de álcool 47 e de lactato 48 são exemplos de sistemas em que este mecanismo catalítico é observado.…”

Section: Efeitos Quânticos E Dinâmicosunclassified

Uma perspectiva computacional sobre catálise enzimática

Arantes¹

2008

Quím. Nova

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Recebido em 24/11/06; aceito em 18/5/07; publicado na web em 19/12/07 A COMPUTATIONAL PERSPECTIVE ON ENZYMATIC CATALYSIS. Enzymes are extremely efficient catalysts. Here, part of the mechanisms proposed to explain this catalytic power will be compared to quantitative experimental results and computer simulations. Influence of the enzymatic environment over species along the reaction coordinate will be analysed. Concepts of transition state stabilisation and reactant destabilisation will be confronted. Divided site model and near-attack conformation hypotheses will also be discussed. Molecular interactions such as covalent catalysis, general acid-base catalysis, electrostatics, entropic effects, steric hindrance, quantum and dynamical effects will also be analysed as sources of catalysis. Reaction mechanisms, in particular that catalysed by protein tyrosine phosphatases, illustrate the concepts.Keywords: enzymatic catalysis; computer simulation; reaction mechanism. INTRODUÇÃOEnzimas são catalisadores de extraordinária eficiência. Os aumentos de velocidade de reações alcançados por enzimas podem chegar a vinte ordens de magnitude 1 ! Por outro lado, enzimas possuem uma grande especificidade pelos substratos, sua atividade é controlável e totalmente seletiva.Sob uma perspectiva teórica, a sugestão de Fischer 2 , conhecida como a hipótese da "chave e fechadura", foi a primeira proposta para explicar o poder catalítico das enzimas. Com o advento da teoria do estado de transição 3 nos anos 1930, Pauling 4 propôs que esta espécie seria preferencialmente ligada pelo sítio ativo enzimático. Já em 1969, Jencks 5 escreveu que "o estudo dos mecanismos moleculares de catálise enzimática é necessariamente empírico e qualitativo". No entanto, nos últimos 30 anos, simulações computacionais que permitem determinações quantitativas de propriedades termodinâmicas têm alterado este panorama, apontando e quantificando os mecanismos catalíticos empregados por enzimas.Cabem aqui duas definições. O termo "mecanismo catalítico" é usado para descrever as forças ou interações microscópicas utilizadas pelas enzimas para amplificar a velocidade de reações. Já "mecanismo de reação" é a seqüência de transformações (quebra e formação de ligações químicas) e mudanças de estrutura do complexo enzimático observadas ao longo do progresso da reação.Diversos mecanismos catalíticos já foram propostos para explicar as acelerações enzimáticas em nível microscópico. Por exemplo, Menger contabilizou 21 teorias sobre catálise enzimática 6 . Este número é elevado em conseqüência de diferentes interpretações semânticas e imprecisas definições de quantidades termodinâmicas nas teorias propostas, e também porque a maior parte destas teorias não foi (ou não pode ser) testada quantitativamente. Portanto, há muita controvérsia sobre a importância de cada um dos diferentes mecanismos e teorias propostos para explicar o poder catalítico das enzimas 7-9 . Sem dúvida, cada enzima possui sua própria "receita" 6 para catálise, em que uma combinação das interações prop...

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Tunneling and Dynamics in Enzymatic Hydride Transfer

Cited by 311 publications

References 119 publications

State transitions and decoherence in the avian compass

State transitions and decoherence in the avian compass

Contribution of Flavin Covalent Linkage with Histidine 99 to the Reaction Catalyzed by Choline Oxidase

Uma perspectiva computacional sobre catálise enzimática

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