Combined experimental and theoretical study of Coelenterazine chemiluminescence in aqueous solution

Lourenço, João; Silva, Joaquim C. G. Esteves da; Silva, Luís Pinto da

doi:10.1016/j.jlumin.2017.10.025

Cited by 19 publications

(17 citation statements)

References 50 publications

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“…The outward movement of the α4 helix has an immediate effect on the opening of the access tunnel and increasing of the buried cavity’s volume, thus facilitating binding of the bulky substrate CTZ. However, once CTZ is bound inside of the active site cavity, the protein has to provide tight binding of the molecule inside it and provide a desolvated environment for the subsequent monooxygenation reaction and bioluminescence to occur 33 , 34 . If the excited product of the reaction, CEI, would not be tightly bound, the energy would probably not be released in the form of light during decay to the ground state, but in another form, e.g., heat.…”

Section: Discussionmentioning

confidence: 99%

Engineering the protein dynamics of an ancestral luciferase

et al. 2021

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Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral protein AncHLD-RLuc which catalyses both dehalogenase and luciferase reactions. Insertion-deletion (InDel) backbone mutagenesis of AncHLD-RLuc challenged the scaffold dynamics. Screening for both activities reveals InDel mutations localized in three distinct regions that lead to altered protein dynamics (based on crystallographic B-factors, hydrogen exchange, and molecular dynamics simulations). An anisotropic network model highlights the importance of the conformational flexibility of a loop-helix fragment of Renilla luciferases for ligand binding. Transplantation of this dynamic fragment leads to lower product inhibition and highly stable glow-type bioluminescence. The success of our approach suggests that a strategy comprising (i) constructing a stable and evolvable template, (ii) mapping functional regions by backbone mutagenesis, and (iii) transplantation of dynamic features, can lead to functionally innovative proteins.

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Section: Discussionmentioning

confidence: 99%

Engineering the protein dynamics of an ancestral luciferase

et al. 2021

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“…These studies have then validated the use of Clz as a reliable approach for the sensitive and dynamic sensing of superoxide anion [29]. However, CL reactions tend to possess lower light-emitting intensities in aqueous solution due to energy loss to water molecules [38,39], and Clz is not an exception [28]. Thus, superoxide anion sensing would benefit from Clz-based CL reactions with enhanced emission in aqueous solutions.…”

Section: Introductionmentioning

confidence: 93%

“…Around 80% of all bioluminescent organisms are present in the oceans and the majority of them employ Clz and other related imidazopyrazinones as BL substrates [27]. Clz itself is capable both of BL (in the presence of either luciferase enzymes or photoproteins) [2] and CL (triggered by oxygenation without an enzyme/photoprotein) [28][29][30]. The CL and BL reactions of Clz generally follow a two-step mechanism [1,2,[12][13][14][21][22][23][24][25][26][27][28][29][30]: there is an oxygenation of the imidazopyrazinone core leading to the formation of the high-energy peroxide intermediate, dioxetanone, which is quite unstable and undergoes thermolysis almost instantly.…”

Section: Introductionmentioning

confidence: 99%

Development of a Coelenterazine Derivative with Enhanced Superoxide Anion-Triggered Chemiluminescence in Aqueous Solution

et al. 2022

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Superoxide anion is a reactive oxygen species (ROS) of biological interest. More specifically, it plays a role in intra- and intercellular signaling, besides being associated with conditions such as inflammation and cancer. Given this, efforts have been made by the research community to devise new sensing strategies for this ROS species. Among them, the chemiluminescent reaction of marine Coelenterazine has been employed as a sensitive and dynamic probing approach. Nevertheless, chemiluminescent reactions are typically associated with lower emissions in aqueous solutions. Herein, here we report the synthesis of a new Coelenterazine derivative with the potential for superoxide anion sensing. Namely, this novel compound is capable of chemiluminescence in a dose-dependent manner when triggered by this ROS species. More importantly, the light-emission intensities provided by this derivative were relevantly enhanced (intensities 2.13 × 101 to 1.11 × 104 times higher) in aqueous solutions at different pH conditions when compared to native Coelenterazine. The half-life of the chemiluminescent signal is also greatly increased for the derivative. Thus, a new chemiluminescence molecule with significant potential for superoxide anion sensing was discovered and reported for the first time.

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“…In the past, the chemiluminescence properties of coelenterazine ( 1 ) and some of its analogues have been the focus of many studies [25] . The final concentration of the compounds used in these experiments is always low, varying between 1 μ m , [25e] 3 μ m , [25i] 10 μ m, [25a,c,d,f] or in two instances 50 μ m [25g,h] . We quickly found out the reason as, at much higher concentration (i.e.…”

Section: Resultsmentioning

confidence: 91%

Core‐Modified Coelenterazine Luciferin Analogues: Synthesis and Chemiluminescence Properties

Gagnot

Hervin

Coutant

et al. 2020

Chemistry A European J

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HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Copyright

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Combined experimental and theoretical study of Coelenterazine chemiluminescence in aqueous solution

Cited by 19 publications

References 50 publications

Engineering the protein dynamics of an ancestral luciferase

Engineering the protein dynamics of an ancestral luciferase

Development of a Coelenterazine Derivative with Enhanced Superoxide Anion-Triggered Chemiluminescence in Aqueous Solution

Core‐Modified Coelenterazine Luciferin Analogues: Synthesis and Chemiluminescence Properties

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