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Michael W Parker - One of the best experts on this subject based on the ideXlab platform.
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reaction mechanism of the bioluminescent protein mnemiopsin1 revealed by x ray crystallography and qm mm simulations
Journal of Biological Chemistry, 2019Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Reza H. Sajedi, Majid Taghdir, Michael A Gorman, Hossein Naderimanesh, Michael W ParkerAbstract:Bioluminescence of a variety of marine organisms, mostly cnidarians and ctenophores, is carried out by Ca2+-dependent photoproteins. The mechanism of light emission operates via the same reaction in both animal families. Despite numerous studies on the ctenophore photoprotein family, the detailed catalytic mechanism and arrangement of amino acid residues surrounding the chromophore in this family are a mystery. Here, we report the crystal structure of Cd2+-loaded apo-mnemiopsin1, a member of the ctenophore family, at 2.15 A resolution and used quantum mechanics/molecular mechanics (QM/MM) to investigate its reaction mechanism. The simulations suggested that an Asp-156-Arg-39-Tyr-202 triad creates a hydrogen-bonded network to facilitate the transfer of a proton from the 2-Hydroperoxy Group of the chromophore coelenterazine to bulk solvent. We identified a water molecule in the coelenteramide-binding cavity that forms a hydrogen bond with the amide nitrogen atom of coelenteramide, which, in turn, is hydrogen-bonded via another water molecule to Tyr-131. This observation supports the hypothesis that the function of the coelenteramide-bound water molecule is to catalyze the 2-Hydroperoxycoelenterazine decarboxylation reaction by protonation of a dioxetanone anion, thereby triggering the bioluminescence reaction in the ctenophore photoprotein family.
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Suggested mechanism for initiating of the reaction in the ctenophore family.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A D158-R41-Y204 triad around the 2- Hydroperoxy Group of coelenterazine forms a hydrogen-bonded network that could shuttle a proton from the 2- Hydroperoxy Group to bulk solvent.
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Induced fit docking study on substrate binding mode.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A) Cutaway view of the berovin cavity showing coelenterazine occupied in. B) Close-up of the amino acid residues around the 2- Hydroperoxy Group of coelenterazine.
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QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract: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 C3 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.
Michael A Gorman - One of the best experts on this subject based on the ideXlab platform.
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reaction mechanism of the bioluminescent protein mnemiopsin1 revealed by x ray crystallography and qm mm simulations
Journal of Biological Chemistry, 2019Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Reza H. Sajedi, Majid Taghdir, Michael A Gorman, Hossein Naderimanesh, Michael W ParkerAbstract:Bioluminescence of a variety of marine organisms, mostly cnidarians and ctenophores, is carried out by Ca2+-dependent photoproteins. The mechanism of light emission operates via the same reaction in both animal families. Despite numerous studies on the ctenophore photoprotein family, the detailed catalytic mechanism and arrangement of amino acid residues surrounding the chromophore in this family are a mystery. Here, we report the crystal structure of Cd2+-loaded apo-mnemiopsin1, a member of the ctenophore family, at 2.15 A resolution and used quantum mechanics/molecular mechanics (QM/MM) to investigate its reaction mechanism. The simulations suggested that an Asp-156-Arg-39-Tyr-202 triad creates a hydrogen-bonded network to facilitate the transfer of a proton from the 2-Hydroperoxy Group of the chromophore coelenterazine to bulk solvent. We identified a water molecule in the coelenteramide-binding cavity that forms a hydrogen bond with the amide nitrogen atom of coelenteramide, which, in turn, is hydrogen-bonded via another water molecule to Tyr-131. This observation supports the hypothesis that the function of the coelenteramide-bound water molecule is to catalyze the 2-Hydroperoxycoelenterazine decarboxylation reaction by protonation of a dioxetanone anion, thereby triggering the bioluminescence reaction in the ctenophore photoprotein family.
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Suggested mechanism for initiating of the reaction in the ctenophore family.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A D158-R41-Y204 triad around the 2- Hydroperoxy Group of coelenterazine forms a hydrogen-bonded network that could shuttle a proton from the 2- Hydroperoxy Group to bulk solvent.
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Induced fit docking study on substrate binding mode.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A) Cutaway view of the berovin cavity showing coelenterazine occupied in. B) Close-up of the amino acid residues around the 2- Hydroperoxy Group of coelenterazine.
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QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract: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 C3 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.
Kenji Matsui - One of the best experts on this subject based on the ideXlab platform.
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n hexanal and z 3 hexenal are generated from arachidonic acid and linolenic acid by a lipoxygenase in marchantia polymorpha l
Bioscience Biotechnology and Biochemistry, 2017Co-Authors: Medhat M Tawfik, Takao Koeduka, Katsuyuki T. Yamato, Takayuki Kohchi, Kenji MatsuiAbstract:Most terrestrial plants form green leaf volatiles (GLVs), which are mainly composed of six-carbon (C6) compounds. In our effort to study the distribution of the ability of lipoxygenase (LOX) to form GLVs, we found that a liverwort, Marchantia polymorpha, formed n-hexanal and (Z)-3-hexenal. Some LOXs execute a secondary reaction to form short chain volatiles. One of the LOXs from M. polymorpha (MpLOX7) oxygenized arachidonic and α-linolenic acids at almost equivalent efficiency and formed C6-aldehydes during its catalysis; these are likely formed from hydroperoxides of arachidonic and α-linolenic acids, with a cleavage of the bond between carbon at the base of the Hydroperoxy Group and carbon of double bond, which is energetically unfavorable. These lines of evidence suggest that one of the LOXs in liverwort employs an unprecedented reaction to form C6 aldehydes as by-products of its reaction with fatty acid substrates.
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n-Hexanal and (Z)-3-hexenal are generated from arachidonic acid and linolenic acid by a lipoxygenase in Marchantia polymorpha L.
2017Co-Authors: Medhat M Tawfik, Takao Koeduka, Katsuyuki T. Yamato, Takayuki Kohchi, Kenji MatsuiAbstract:Most terrestrial plants form green leaf volatiles (GLVs), which are mainly composed of six-carbon (C6) compounds. In our effort to study the distribution of the ability of lipoxygenase (LOX) to form GLVs, we found that a liverwort, Marchantia polymorpha, formed n-hexanal and (Z)-3-hexenal. Some LOXs execute a secondary reaction to form short chain volatiles. One of the LOXs from M. polymorpha (MpLOX7) oxygenized arachidonic and α-linolenic acids at almost equivalent efficiency and formed C6-aldehydes during its catalysis; these are likely formed from hydroperoxides of arachidonic and α-linolenic acids, with a cleavage of the bond between carbon at the base of the Hydroperoxy Group and carbon of double bond, which is energetically unfavorable. These lines of evidence suggest that one of the LOXs in liverwort employs an unprecedented reaction to form C6 aldehydes as by-products of its reaction with fatty acid substrates. One of Marchantia polymorpha lipoxygenases forms six-carbon aldehydes as by-products.
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on the specificity of lipid hydroperoxide fragmentation by fatty acid hydroperoxide lyase from arabidopsis thaliana
Journal of Plant Physiology, 2003Co-Authors: Romy Kandzia, Kenji Matsui, Michael Stumpe, Ekkehardt Berndt, Marlena Szalata, Ivo FeussnerAbstract:Summary Fatty acid hydroperoxide lyase (HPL) is a membrane associated P450 enzyme that cleaves fatty acid hydroperoxides into aldehydes and ω-xo fatty acids. One of the major products of this reaction is (3 Z )-hexenal. It is a constituent of many fresh smelling fruit aromas. For its biotechnological production and because of the lack of structural data on the HPL enzyme family, we investigated the mechanistic reasons for the substrate specificity of HPL by using various structural analogues of HPL substrates. To approach this 13-HPL from Arabidopsis thaliana was cloned and expressed in E. coli utilising a His-Tag expression vector. The fusion protein was purified by affinity chromatography from the E. coli membrane fractions and its pH optimum was detected to be pH 7.2. Then, HPL activity against the respective (9 S )- and (13 S )-hydroperoxides derived either from linoleic, α-linolenic or γ-linolenic acid, respectively, as well as that against the corresponding methyl esters was analysed. Highest enzyme activity was observed with the (13 S )-hydroperoxide of α-linolenic acid (13α-HPOT) followed by that with its methyl ester. Most interestingly, when the Hydroperoxy isomers of γ-linolenic acid were tested as substrates, 9γ-HPOT and not 13γ-HPOT was found to be a better substrate of the enzyme. Taken together from these studies on the substrate specificity it is concluded that At13HPL may not recognise the absolute position of the Hydroperoxy Group within the substrate, but shows highest activities against substrates with a (1 Z ,4 S ,5 E ,7 Z )-4-Hydroperoxy-1,5,7-triene motif. Thus, At13HPL may not only be used for the production of C 6 -derived volatiles, but depending on the substrate may be further used for the production of C 9 -derived volatiles as well.
Maryam Molakarimi - One of the best experts on this subject based on the ideXlab platform.
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reaction mechanism of the bioluminescent protein mnemiopsin1 revealed by x ray crystallography and qm mm simulations
Journal of Biological Chemistry, 2019Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Reza H. Sajedi, Majid Taghdir, Michael A Gorman, Hossein Naderimanesh, Michael W ParkerAbstract:Bioluminescence of a variety of marine organisms, mostly cnidarians and ctenophores, is carried out by Ca2+-dependent photoproteins. The mechanism of light emission operates via the same reaction in both animal families. Despite numerous studies on the ctenophore photoprotein family, the detailed catalytic mechanism and arrangement of amino acid residues surrounding the chromophore in this family are a mystery. Here, we report the crystal structure of Cd2+-loaded apo-mnemiopsin1, a member of the ctenophore family, at 2.15 A resolution and used quantum mechanics/molecular mechanics (QM/MM) to investigate its reaction mechanism. The simulations suggested that an Asp-156-Arg-39-Tyr-202 triad creates a hydrogen-bonded network to facilitate the transfer of a proton from the 2-Hydroperoxy Group of the chromophore coelenterazine to bulk solvent. We identified a water molecule in the coelenteramide-binding cavity that forms a hydrogen bond with the amide nitrogen atom of coelenteramide, which, in turn, is hydrogen-bonded via another water molecule to Tyr-131. This observation supports the hypothesis that the function of the coelenteramide-bound water molecule is to catalyze the 2-Hydroperoxycoelenterazine decarboxylation reaction by protonation of a dioxetanone anion, thereby triggering the bioluminescence reaction in the ctenophore photoprotein family.
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Suggested mechanism for initiating of the reaction in the ctenophore family.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A D158-R41-Y204 triad around the 2- Hydroperoxy Group of coelenterazine forms a hydrogen-bonded network that could shuttle a proton from the 2- Hydroperoxy Group to bulk solvent.
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Induced fit docking study on substrate binding mode.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A) Cutaway view of the berovin cavity showing coelenterazine occupied in. B) Close-up of the amino acid residues around the 2- Hydroperoxy Group of coelenterazine.
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QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract: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 C3 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.
Reza H. Sajedi - One of the best experts on this subject based on the ideXlab platform.
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reaction mechanism of the bioluminescent protein mnemiopsin1 revealed by x ray crystallography and qm mm simulations
Journal of Biological Chemistry, 2019Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Reza H. Sajedi, Majid Taghdir, Michael A Gorman, Hossein Naderimanesh, Michael W ParkerAbstract:Bioluminescence of a variety of marine organisms, mostly cnidarians and ctenophores, is carried out by Ca2+-dependent photoproteins. The mechanism of light emission operates via the same reaction in both animal families. Despite numerous studies on the ctenophore photoprotein family, the detailed catalytic mechanism and arrangement of amino acid residues surrounding the chromophore in this family are a mystery. Here, we report the crystal structure of Cd2+-loaded apo-mnemiopsin1, a member of the ctenophore family, at 2.15 A resolution and used quantum mechanics/molecular mechanics (QM/MM) to investigate its reaction mechanism. The simulations suggested that an Asp-156-Arg-39-Tyr-202 triad creates a hydrogen-bonded network to facilitate the transfer of a proton from the 2-Hydroperoxy Group of the chromophore coelenterazine to bulk solvent. We identified a water molecule in the coelenteramide-binding cavity that forms a hydrogen bond with the amide nitrogen atom of coelenteramide, which, in turn, is hydrogen-bonded via another water molecule to Tyr-131. This observation supports the hypothesis that the function of the coelenteramide-bound water molecule is to catalyze the 2-Hydroperoxycoelenterazine decarboxylation reaction by protonation of a dioxetanone anion, thereby triggering the bioluminescence reaction in the ctenophore photoprotein family.
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Suggested mechanism for initiating of the reaction in the ctenophore family.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A D158-R41-Y204 triad around the 2- Hydroperoxy Group of coelenterazine forms a hydrogen-bonded network that could shuttle a proton from the 2- Hydroperoxy Group to bulk solvent.
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Induced fit docking study on substrate binding mode.
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract:A) Cutaway view of the berovin cavity showing coelenterazine occupied in. B) Close-up of the amino acid residues around the 2- Hydroperoxy Group of coelenterazine.
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QM/MM simulations provide insight into the mechanism of bioluminescence triggering in ctenophore photoproteins
2017Co-Authors: Maryam Molakarimi, Ammar Mohseni, Zaiddodine Pashandi, Majid Taghdir, Michael A Gorman, Michael W Parker, Hossein Naderi-manesh, Reza H. SajediAbstract: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 C3 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.
