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QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins

Photoproteins are responsible for light emission in a variety of marine ctenophores and coelenterates. The mechanism of light emission in both families occurs via the same reaction. However, the arrangement of amino acid residues surrounding the chromophore, and the catalytic mechanism of light emis...

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Autores principales: Molakarimi, Maryam, Mohseni, Ammar, Taghdir, Majid, Pashandi, Zaiddodine, Gorman, Michael A., Parker, Michael W., Naderi-Manesh, Hossein, Sajedi, Reza H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544205/
https://www.ncbi.nlm.nih.gov/pubmed/28777808
http://dx.doi.org/10.1371/journal.pone.0182317
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author Molakarimi, Maryam
Mohseni, Ammar
Taghdir, Majid
Pashandi, Zaiddodine
Gorman, Michael A.
Parker, Michael W.
Naderi-Manesh, Hossein
Sajedi, Reza H.
author_facet Molakarimi, Maryam
Mohseni, Ammar
Taghdir, Majid
Pashandi, Zaiddodine
Gorman, Michael A.
Parker, Michael W.
Naderi-Manesh, Hossein
Sajedi, Reza H.
author_sort Molakarimi, Maryam
collection PubMed
description Photoproteins are responsible for light emission in a variety of marine ctenophores and coelenterates. The mechanism of light emission in both families occurs via the same reaction. However, the arrangement of amino acid residues surrounding the chromophore, and the catalytic mechanism of light emission is unknown for the ctenophore photoproteins. In this study, we used quantum mechanics/molecular mechanics (QM/MM) and site-directed mutagenesis studies to investigate the details of the catalytic mechanism in berovin, a member of the ctenophore family. In the absence of a crystal structure of the berovin-substrate complex, molecular docking was used to determine the binding mode of the protonated (2-hydroperoxy) and deprotonated (2-peroxy anion) forms of the substrate to berovin. A total of 13 mutants predicted to surround the binding site were targeted by site-directed mutagenesis which revealed their relative importance in substrate binding and catalysis. Molecular dynamics simulations and MM-PBSA (Molecular Mechanics Poisson-Boltzmann/surface area) calculations showed that electrostatic and polar solvation energy are +115.65 and -100.42 kcal/mol in the deprotonated form, respectively. QM/MM calculations and pKa analysis revealed the deprotonated form of substrate is unstable due to the generation of a dioxetane intermediate caused by nucleophilic attack of the substrate peroxy anion at its C(3) position. This work also revealed that a hydrogen bonding network formed by a D158- R41-Y204 triad could be responsible for shuttling the proton from the 2- hydroperoxy group of the substrate to bulk solvent.
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spelling pubmed-55442052017-08-12 QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins Molakarimi, Maryam Mohseni, Ammar Taghdir, Majid Pashandi, Zaiddodine Gorman, Michael A. Parker, Michael W. Naderi-Manesh, Hossein Sajedi, Reza H. PLoS One Research Article Photoproteins are responsible for light emission in a variety of marine ctenophores and coelenterates. The mechanism of light emission in both families occurs via the same reaction. However, the arrangement of amino acid residues surrounding the chromophore, and the catalytic mechanism of light emission is unknown for the ctenophore photoproteins. In this study, we used quantum mechanics/molecular mechanics (QM/MM) and site-directed mutagenesis studies to investigate the details of the catalytic mechanism in berovin, a member of the ctenophore family. In the absence of a crystal structure of the berovin-substrate complex, molecular docking was used to determine the binding mode of the protonated (2-hydroperoxy) and deprotonated (2-peroxy anion) forms of the substrate to berovin. A total of 13 mutants predicted to surround the binding site were targeted by site-directed mutagenesis which revealed their relative importance in substrate binding and catalysis. Molecular dynamics simulations and MM-PBSA (Molecular Mechanics Poisson-Boltzmann/surface area) calculations showed that electrostatic and polar solvation energy are +115.65 and -100.42 kcal/mol in the deprotonated form, respectively. QM/MM calculations and pKa analysis revealed the deprotonated form of substrate is unstable due to the generation of a dioxetane intermediate caused by nucleophilic attack of the substrate peroxy anion at its C(3) position. This work also revealed that a hydrogen bonding network formed by a D158- R41-Y204 triad could be responsible for shuttling the proton from the 2- hydroperoxy group of the substrate to bulk solvent. Public Library of Science 2017-08-04 /pmc/articles/PMC5544205/ /pubmed/28777808 http://dx.doi.org/10.1371/journal.pone.0182317 Text en © 2017 Molakarimi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Molakarimi, Maryam
Mohseni, Ammar
Taghdir, Majid
Pashandi, Zaiddodine
Gorman, Michael A.
Parker, Michael W.
Naderi-Manesh, Hossein
Sajedi, Reza H.
QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
title QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
title_full QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
title_fullStr QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
title_full_unstemmed QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
title_short QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
title_sort qm/mm simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544205/
https://www.ncbi.nlm.nih.gov/pubmed/28777808
http://dx.doi.org/10.1371/journal.pone.0182317
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