scholarly journals Refining the reaction mechanism of O2towards its co-substrate in cofactor-free dioxygenases

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2805 ◽  
Author(s):  
Pedro J. Silva
Keyword(s):  
Electron Transfer ◽  
Active Site ◽  
Quantum Chemical ◽  
Potential Energy Surfaces ◽  
Direct Electron Transfer ◽  
Minimum Energy ◽  
Urate Oxidase ◽  
Redox Potentials ◽  
Deprotonated Form ◽  
Quantum Chemical Computations

Cofactor-less oxygenases perform challenging catalytic reactions between singlet co-substrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In 1-H-3-hydroxy-4-oxoquinaldine-2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from co-substrate to O2followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the co-substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.

scholarly journals Refining the reaction mechanism of O2 towards its substrate in cofactor-free dioxygenases

2016 ◽  
Author(s):  
Pedro J Silva
Keyword(s):  
Electron Transfer ◽  
Active Site ◽  
Quantum Chemical ◽  
Potential Energy Surfaces ◽  
Direct Electron Transfer ◽  
Minimum Energy ◽  
Urate Oxidase ◽  
Redox Potentials ◽  
Deprotonated Form ◽  
Quantum Chemical Computations

Cofactor-less oxygenases perform challenging catalytic reactions between singlet substrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In bacterial ring-cleaving 2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from substrate to O2 followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.

scholarly journals Refining the reaction mechanism of O2 towards its substrate in cofactor-free dioxygenases

2016 ◽  
Author(s):  
Pedro J Silva
Keyword(s):  
Electron Transfer ◽  
Active Site ◽  
Quantum Chemical ◽  
Potential Energy Surfaces ◽  
Direct Electron Transfer ◽  
Minimum Energy ◽  
Urate Oxidase ◽  
Redox Potentials ◽  
Deprotonated Form ◽  
Quantum Chemical Computations

Cofactor-less oxygenases perform challenging catalytic reactions between singlet substrates and triplet oxygen, in spite of apparently violating the spin-conservation rule. In bacterial ring-cleaving 2,4-dioxygenase, the active site has been suggested by quantum chemical computations to fine tune triplet oxygen reactivity, allowing it to interact rapidly with its singlet substrate without the need for spin inversion, and in urate oxidase the reaction is thought to proceed through electron transfer from the deprotonated substrate to an aminoacid sidechain, which then feeds the electron to the oxygen molecule. In this work, we perform additional quantum chemical computations on these two systems to elucidate several intriguing features unaddressed by previous workers. These computations establish that in both enzymes the reaction proceeds through direct electron transfer from substrate to O2 followed by radical recombination, instead of minimum-energy crossing points between singlet and triplet potential energy surfaces without formal electron transfer. The active site does not affect the reactivity of oxygen directly but is crucial for the generation of the deprotonated form of the substrates, which have redox potentials far below those of their protonated forms and therefore may transfer electrons to oxygen without sizeable thermodynamic barriers. This mechanism seems to be shared by most cofactor-less oxidases studied so far.

scholarly journals One-megadalton metalloenzyme complex inGeobacter metallireducensinvolved in benzene ring reduction beyond the biological redox window

2019 ◽  
Vol 116 (6) ◽  
pp. 2259-2264 ◽  
Author(s):  
Simona G. Huwiler ◽  
Claudia Löffler ◽  
Sebastian E. L. Anselmann ◽  
Hans-Joachim Stärk ◽  
Martin von Bergen ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Benzene Ring ◽  
Active Site ◽  
Anaerobic Bacterium ◽  
Class Ii ◽  
High Molecular Mass ◽  
Redox Potentials ◽  
Geobacter Metallireducens ◽  
Redox Couples ◽  
Biological Electron Transfer

Reversible biological electron transfer usually occurs between redox couples at standard redox potentials ranging from +0.8 to −0.5 V. Dearomatizing benzoyl-CoA reductases (BCRs), key enzymes of the globally relevant microbial degradation of aromatic compounds at anoxic sites, catalyze a biological Birch reduction beyond the negative limit of this redox window. The structurally characterized BamBC subunits of class II BCRs accomplish benzene ring reduction at an active-site tungsten cofactor; however, the mechanism and components involved in the energetic coupling of endergonic benzene ring reduction have remained hypothetical. We present a 1-MDa, membrane-associated, Bam[(BC)2DEFGHI]2complex from the anaerobic bacteriumGeobacter metallireducensharboring 4 tungsten, 4 zinc, 2 selenocysteines, 6 FAD, and >50 FeS cofactors. The results suggest that class II BCRs catalyze electron transfer to the aromatic ring, yielding a cyclic 1,5-dienoyl-CoA via two flavin-based electron bifurcation events. This work expands our knowledge of energetic couplings in biology by high-molecular-mass electron bifurcating machineries.

scholarly journals Recent Advances in the Direct Electron Transfer-Enabled Enzymatic Fuel Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Sooyoun Yu ◽  
Nosang V. Myung
Keyword(s):  
Electron Transfer ◽  
Fuel Cell ◽  
Active Site ◽  
Electrode Surface ◽  
Oxidation Reaction ◽  
Direct Electron Transfer ◽  
Implantable Devices ◽  
Protein Matrix ◽  
Enzyme Active Site ◽  
Enzymatic Fuel Cell

Direct electron transfer (DET), which requires no mediator to shuttle electrons from enzyme active site to the electrode surface, minimizes complexity caused by the mediator and can further enable miniaturization for biocompatible and implantable devices. However, because the redox cofactors are typically deeply embedded in the protein matrix of the enzymes, electrons generated from oxidation reaction cannot easily transfer to the electrode surface. In this review, methods to improve the DET rate for enhancement of enzymatic fuel cell performances are summarized, with a focus on the more recent works (past 10 years). Finally, progress on the application of DET-enabled EFC to some biomedical and implantable devices are reported.

scholarly journals Electrochemical redox transformations of T1 and T2 copper sites in native Trametes hirsuta laccase at gold electrode

2005 ◽  
Vol 385 (3) ◽  
pp. 745-754 ◽  
Author(s):  
Sergey SHLEEV ◽  
Andreas CHRISTENSON ◽  
Vladimir SEREZHENKOV ◽  
Dosymzhan BURBAEV ◽  
Alexander YAROPOLOV ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Gold Electrode ◽  
Direct Electron Transfer ◽  
High Potential ◽  
Redox Potentials ◽  
Hydrogen Electrode ◽  
Trametes Hirsuta ◽  
Redox Transformations ◽  
Copper Site ◽  
Copper Sites

Mediatorless, electrochemically driven, redox transformations of T1 (type 1) and T2 copper sites in Trametes hirsuta laccase were studied by cyclic voltammetry and spectroelectrochemical redox titrations using bare gold electrode. DET (direct electron transfer) between the electrode and the enzyme was observed under anaerobic conditions. From analysis of experimental data it is concluded that the T2 copper site is in DET contact with gold. It was found that electron transfer between the gold surface and the T1 copper site progresses through the T2 copper site. From EPR measurements and electrochemical data it is proposed that the redox potential of the T2 site for high-potential ‘blue’ laccase is equal to about 400 mV versus NHE (normal hydrogen electrode) at pH 6.5. The hypothesis that the redox potentials of the T2 copper sites in low- and high-potential laccases/oxidases from totally different sources might be very similar, i.e. approx. 400 mV, is discussed.

scholarly journals Will 1,2-dihydro-1,2-azaborine-based drugs resist metabolism by cytochrome P450 compound I?

2016 ◽  
Author(s):  
Pedro J Silva
Keyword(s):  
Cytochrome P450 ◽  
Active Site ◽  
Quantum Chemical ◽  
Compound I ◽  
Pharmaceutical Applications ◽  
Steric Crowding ◽  
Binding Pockets ◽  
Quantum Chemical Computations ◽  
Limited Usefulness ◽  
Biological Context

1,2-dihydro-1,2-azaborine is a structural and electronic analogue of benzene which is able to occupy benzene-binding pockets in T4 lysozymeand has been proposed as suitable arene-mimicking group for biological and pharmaceutical applications. Its applicability in a biological context requires it to be able to resist modification by xenobiotic-degrading enzymes like the P450 cytochromes. Quantum chemical computations described in this work show that 1,2-dihydro-1,2-azaborine is much more prone to modification by these enzymes than benzene, unless steric crowding of the ring prevents it from reaching the active site, or otherwise only allows reaction at the very sluggish C4-position. This novel heterocyclic compound is therefore expected to be of limited usefulness as an aryl bioisostere.

Dissociative electron transfer in polychlorinated aromatics. Reduction potentials from convolution analysis and quantum chemical calculations

2016 ◽  
Vol 18 (32) ◽  
pp. 22573-22582 ◽  
Author(s):  
Piotr P. Romańczyk ◽  
Grzegorz Rotko ◽  
Stefan S. Kurek
Keyword(s):  
Electron Transfer ◽  
Quantum Chemical Calculations ◽  
Quantum Chemical ◽  
Redox Potentials ◽  
Dissociative Electron Transfer ◽  
Reduction Potentials ◽  
Polychlorinated Benzenes

The combination of convolution analysis and quantum-chemical calculations at DFT and CCSD(T)-F12 levels allows the determination of standard redox potentials and the mechanism type of dissociative ET in environmentally relevant polychlorinated benzenes.

Sign in / Sign up

Export Citation Format

Share Document