Impact of Local Electrostatics on the Redox Properties of Tryptophan Radicals in Azurin: Implications for Redox-Active Tryptophans in Proton-Coupled Electron Transfer

Tyson, Kristin; Davis, Amanda; Norris, Jessica L.; Bartolotti, Libero J.; Hvastkovs, Eli G.; Offenbacher, Adam R.

doi:10.1021/acs.jpclett.0c00614

Cited by 13 publications

(36 citation statements)

References 45 publications

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“…The lower estimate of the TRP pair is in line with observations for π-stacked guanine potential shifts ( 62 , 63 ). The lack of solvent access to the tryptophan dimer creates an electrostatic environment that makes it likely that their true reduction potential is even lower ( 64 ), possibly facilitating even faster hole transfer than estimated in our analysis.…”

Section: Resultsmentioning

confidence: 93%

Oxalate decarboxylase uses electron hole hopping for catalysis

Pastore

Teo

Montoya

et al. 2021

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 93%

Oxalate decarboxylase uses electron hole hopping for catalysis

Pastore

Teo

Montoya

et al. 2021

Journal of Biological Chemistry

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“…The one-electron reduction potential for the cation radical (Trp •+ /Trp) is about +1.2 V versus NHE based on l -Trp; 62 , 63 a recent measurement of the electrochemical potential for W48 in ZnAzW48 reported +0.952 V vs. NHE. 15 The E 0,0 energy between the ground state and the lowest-lying triplet is 3.0 eV (corresponding to 410 nm phosphorescence). These energies result in the availability of about 2 V of potential for the triplet to reduce an acceptor.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have characterized the tryptophan neutral radical in a blue-copper protein, azurin, of Pseudomonas aeruginosa . − Azurin is a 128-residue protein with eight β-strands arranged in a Greek key motif and a small α-helical segment. The metal-binding site is located at one end of the protein, with a single native tryptophan residue (W48) buried in a hydrophobic pocket.…”

Section: Introductionmentioning

confidence: 99%

Role of the Triplet State and Protein Dynamics in the Formation and Stability of the Tryptophan Radical in an Apoazurin Mutant

et al. 2022

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The protein, azurin, has enabled the study of the tryptophan radical. Upon UV excitation of tyrosine-deficient apoazurin and in the presence of a Co(III) electron acceptor, the neutral radical (W48•) is formed. The lifetime of W48• in apoazurin is 41 s, which is shorter than the lifetime of several hours in Zn-substituted azurin. Molecular dynamics simulations revealed enhanced fluctuations of apoazurin which likely destabilize W48•. The photophysics of W48 was investigated to probe the precursor state for ET. The phosphorescence intensity was eliminated in the presence of an electron acceptor while the fluorescence was unchanged; this quenching of the phosphorescence is attributed to ET. The kinetics associated with W48• were examined with a model that incorporates intersystem crossing, ET, deprotonation, and decay of the cation radical. The estimated rate constants for ET (6 × 10 6 s –1 ) and deprotonation (3 × 10 5 s –1 ) are in agreement with a photoinduced mechanism where W48• is derived from the triplet state. The triplet as the precursor state for ET was supported by photolysis of apoazurin with 280 nm in the absence and presence of triplet-absorbing 405 nm light. Absorption bands from the neutral radical were observed only in the presence of blue light.

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“…In the presence of the tartaric acid, the H-bond distance between Glu250 and Trp171 increased by 0.9 Å (Figure S16). This would shift the Trp171 towards its protonated state, which has a significantly higher reduction potential than its deprotonated form, 94 hence enhancing the oxidizing power of the Trp171 radical. Indeed, such a hypothesis is well supported by our QM model calculations (see Figure 6).…”

Section: Et From the Lignin Substrate To Trp171 In The Presence Of Th...mentioning

confidence: 99%

“…It was found experimentally that the oxidized Trp has a pKa of 4.5. 94 This implies that at pH=3.06 the oxidized Trp would exist in its protonated form, while at pH=7.39 the oxidized Trp would exist in its neutral radical form. Such a finding agrees with our simulations.…”

Section: Without Tartaric Acidmentioning

confidence: 99%

pH Accelerates the Long-Range Electron Transfer for Lignin Degradation via Second-Sphere H-Bonding Interactions

Fang

Feng

Jiang

et al. 2022

Preprint

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pH plays versatile roles in both biology and chemistry. For instance, pH can regulate the long-range electron transfer (ET) in many proteins. However, the mechanistic basis of many pH-dependent long-range ET processes remain unclear. In this study, we unravel the critical role of pH in accelerating the long-range ET in lignin peroxidase (LiP) using QM/MM MD simulations and the nonadiabatic ET and PCET theories. As a key enzyme involved in lignin degradation, LiP accomplishes the one-electron oxidation of lignin via two consecutive long-range ET reactions: the first one involves ET from Trp171 to the active species of Compound I, affording the Trp171 radical species, while the second one involves ET from the lignin substrate to the Trp171 radical, affording the lignin cation radical species. Our study demonstrates that pH can remarkably modulate the mechanism and kinetics of both ET reactions. Specifically, in the absence of the pH buffer of tartaric acid, our study shows that the first ET leads to a neutral Trp• radical, agreeing with the EPR experiments. Surprisingly, the addition of the tartaric acid stabilizes the Trp-H•+ cation radical via second-sphere H-bonding interactions and accelerates the ET rate for lignin oxidation by several orders of magnitude. These findings are consistent with the experimental information available, which not only expand our understanding on pH-dependent ET reactions in both biology and chemistry, but also provide valuable insights on tryptophan-mediated biological ET reactions.

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Impact of Local Electrostatics on the Redox Properties of Tryptophan Radicals in Azurin: Implications for Redox-Active Tryptophans in Proton-Coupled Electron Transfer

Cited by 13 publications

References 45 publications

Oxalate decarboxylase uses electron hole hopping for catalysis

Oxalate decarboxylase uses electron hole hopping for catalysis

Role of the Triplet State and Protein Dynamics in the Formation and Stability of the Tryptophan Radical in an Apoazurin Mutant

pH Accelerates the Long-Range Electron Transfer for Lignin Degradation via Second-Sphere H-Bonding Interactions

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