QM/MM Molecular Modeling Reveals Mechanism Insights into Flavin Peroxide Formation in Bacterial Luciferase

Lawan, Narin; Tinikul, Ruchanok; Surawatanawong, Panida; Mulholland, Adrian J.; Chaiyen, Pimchai

doi:10.1021/acs.jcim.1c01187

Cited by 12 publications

(13 citation statements)

References 42 publications

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“…Similarly, we used model molecules IM-2 and CH 3 CH 2 CH(OH)OOH in the calculations. For electron donor B, experimental and computational studies have shown that in bacterial luciferase, the histidine residue at position 44 (His44) of the α subunit plays an important role in bacterial BL. , Quite recently, a research also found an important role of different protonation forms of His44 in controlling the reaction mechanism in luciferase catalysis . Based on the protonation forms of histidine, it can be used as a catalytic acid (HIP + ) or catalytic base (HIE).…”

Section: Resultsmentioning

confidence: 99%

“…8,62 Quite recently, a research also found an important role of different protonation forms of His44 in controlling the reaction mechanism in luciferase catalysis. 63 Based on the protonation forms of histidine, it can be used as a catalytic acid (HIP + ) or catalytic base (HIE). In this mechanism, the electron donor B as a catalytic base is considered to be HIE44.…”

Section: Mechanism F: Upper Excited Statementioning

confidence: 99%

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Thorough Understanding of Bioluminophore Production in Bacterial Bioluminescence

Luo

Liu

2022

J. Phys. Chem. A

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Bioluminophore of bioluminescence (BL) comes from the decomposition of peroxide, which is an intermediate produced in the complicated chemical reactions of BL. The peroxide is a dioxetanone in most BL cases and an endoperoxide in fungal BL. The decomposition mechanisms of these two types of peroxides have been exclusively studied. However, the peroxide is a linear organic peroxide in bacterial BL, whose decomposition explanations are quite controversial, and seven mechanisms have been proposed. To thoroughly understand the mechanism of bioluminophore production in bacterial BL, this paper systematically discusses the seven proposed mechanisms via the present computational results and previous experimental and theoretical results. Our research results indicate that the bioluminophore in bacterial BL is produced through the charge-transfer initiated luminescence (CTIL) mechanism. The decomposition mechanism of linear organic peroxide was compared with the decomposition mechanisms of the other two types of peroxides, dioxetanone and endoperoxide. This study is also helpful in understanding the bioluminophore production in other BLs via the decomposition of an organic peroxide, such as dinoflagellate BL.

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Section: Resultsmentioning

confidence: 99%

Section: Mechanism F: Upper Excited Statementioning

confidence: 99%

Thorough Understanding of Bioluminophore Production in Bacterial Bioluminescence

Luo

Liu

2022

J. Phys. Chem. A

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“…Also, molecular dynamic simulations were performed to investigate the behavior of the mentioned atoms ( Lawan et al, 2022 ).…”

Section: Calculation Detailsmentioning

confidence: 99%

Carbon fixation of CO2 via cyclic reactions with borane in gaseous atmosphere leading to formic acid (and metaboric acid); A potential energy surface (PES) study

et al. 2022

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Carbon dioxide (CO2), a stable gaseous species, occupies the troposphere layer of the atmosphere. Following it, the environment gets warmer, and the ecosystem changes as a consequence of disrupting the natural order of our life. Due to this, in the present reasearch, the possibility of carbon fixation of CO2 by using borane was investigated. To conduct this, each of the probable reaction channels between borane and CO2 was investigated to find the fate of this species. The results indicate that among all the channels, the least energetic path for the reaction is reactant complex (RC) to TS (A-1) to Int (A-1) to TS (A-D) to formic acid (and further meta boric acid production from the transformation of boric acid). It shows that use of gaseous borane might lead to controlling these dangerous greenhouse gases which are threatening the present form of life on Earth, our beautiful, fragile home.

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“…Previous information obtained from other C4a-OO (H)-forming enzymes showed that positively charged residues such as His396 C2 in p-hydroxyphenylacetate 3-hydroxylase (C 2 ) from Acinetobacter baumannii [14][15][16], His548 P2O in pyranose-2-oxidase (P2O) from Trametes multicolor [17], Arg329 CHMO in cyclohexanone monooxygenase (CHMO) from Rhodococcus sp. strain HI-31 [18], His44 LuxAB in bacterial luciferase from Vibrio campbellii (LuxAB) [19,20] and His391 DszC in dibenzothiophene monooxygenase (DszC) from Rhodococcus sp. XP [21,22] are key residues for C4a-OO(H) formation and stabilization.…”

Section: Introductionmentioning

confidence: 99%

“…XP [21,22] are key residues for C4a-OO(H) formation and stabilization. Results from kinetic experiments, structural analysis and QM/MM calculations in C 2 , P2O and LuxAB revealed that these residues could provide protons (H + ) to activate dioxygen via the proton-coupled electron transfer (PCET) mechanism [16,17,19]. Thus, the positively charged environment should support the formation and stabilization of C4a-OO(H) in various flavin-dependent enzymes.…”

Section: Introductionmentioning

confidence: 99%

Formation and stabilization of C4a‐hydroperoxy‐FAD by the Arg/Asn pair in HadA monooxygenase

Pimviriyakul

Chaiyen

2022

The FEBS Journal

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HadA monooxygenase catalyses the detoxification of halogenated phenols and nitrophenols via dehalogenation and denitration respectively. C4a‐hydroperoxy‐FAD is a key reactive intermediate wherein its formation, protonation and stabilization reflect enzyme efficiency. Herein, transient kinetics, site‐directed mutagenesis and pH‐dependent behaviours of HadA reaction were employed to identify key features stabilizing C4a‐adducts in HadA. The formation of C4a‐hydroperoxy‐FAD is pH independent, whereas its decay and protonation of distal oxygen are associated with pKa values of 8.5 and 8.4 respectively. These values are correlated with product formation within a pH range of 7.6–9.1, indicating the importance of adduct stabilization to enzymatic efficiency. We identified Arg101 as a key residue for reduced FAD (FADH−) binding and C4a‐hydroperoxy‐FAD formation due to the loss of these abilities as well as enzyme activity in HadAR101A and HadAR101Q. Mutations of the neighbouring Asn447 do not affect the rate of C4a‐hydroperoxy‐FAD formation; however, they impair FADH− binding. The disruption of Arg101/Asn447 hydrogen bond networking in HadAN447A increases the pKa value of C4a‐hydroperoxy‐FAD decay to 9.5; however, this pKa was not altered in HadAN447D (pKa of 8.5). Thus, Arg101/Asn447 pair should provide important interactions for FADH− binding and maintain the pKa associated with H2O2 elimination from C4a‐hydroperoxy‐FAD in HadA. In the presence of substrate, the formation of C4a‐hydroxy‐FAD at the hydroxylation step is pH insensitive, and it dehydrates to form the oxidized FAD with pKa of 7.9. This structural feature might help elucidate how the reactive intermediate was stabilized in other flavin‐dependent monooxygenases.

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QM/MM Molecular Modeling Reveals Mechanism Insights into Flavin Peroxide Formation in Bacterial Luciferase

Cited by 12 publications

References 42 publications

Thorough Understanding of Bioluminophore Production in Bacterial Bioluminescence

Thorough Understanding of Bioluminophore Production in Bacterial Bioluminescence

Carbon fixation of CO2 via cyclic reactions with borane in gaseous atmosphere leading to formic acid (and metaboric acid); A potential energy surface (PES) study

Formation and stabilization of C4a‐hydroperoxy‐FAD by the Arg/Asn pair in HadA monooxygenase

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