The Experts below are selected from a list of 24 Experts worldwide ranked by ideXlab platform

Masha Y. Niv - One of the best experts on this subject based on the ideXlab platform.

  • Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors.
    Frontiers in molecular biosciences, 2018
    Co-Authors: Antonella Pizio, Wolfgang Meyerhof, Maik Behrens, Nitzan Shy, Masha Y. Niv
    Abstract:

    Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallus taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys3.29 and Asn3.36 are suggested as ggTas2r1-specificity-conferring residues; Gln6.55 as ggTas2r2-specificity-conferring residue; Ser5.38 and Gln7.42 as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and Ethylhydrocupreine, was then characterized by combining calcium-imaging experiments and in silico approaches. ggTas2r models were used to virtually screen BitterDB compounds. ~50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested with in vitro and in vivo experiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.

  • Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case
    Scientific Reports, 2017
    Co-Authors: Antonella Pizio, Louisa-marie Kruetzfeldt, Shira Cheled-shoval, Wolfgang Meyerhof, Maik Behrens, Masha Y. Niv
    Abstract:

    Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1. Because of low sequence similarity between ggTas2r1 and crystallized GPCRs (~10% identity, ~30% similarity at most), the combination of computational approaches with site-directed mutagenesis was used to characterize the agonist-bound conformation of ggTas2r1 binding site between TMs 3, 5, 6 and 7. We found that the ligand interactions with N93 in TM3 and/or N247 in TM5, combined with hydrophobic contacts, are typically involved in agonist recognition. Next, the ggTas2r1 structural model was successfully used to identify three quinine analogues (epiquinidine, Ethylhydrocupreine, quinidine) as new ggTas2r1 agonists. The integrated approach validated here may be applicable to additional cases where the sequence identity of the GPCR of interest and the existing experimental structures is low.

Antonella Pizio - One of the best experts on this subject based on the ideXlab platform.

  • Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors.
    Frontiers in molecular biosciences, 2018
    Co-Authors: Antonella Pizio, Wolfgang Meyerhof, Maik Behrens, Nitzan Shy, Masha Y. Niv
    Abstract:

    Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallus taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys3.29 and Asn3.36 are suggested as ggTas2r1-specificity-conferring residues; Gln6.55 as ggTas2r2-specificity-conferring residue; Ser5.38 and Gln7.42 as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and Ethylhydrocupreine, was then characterized by combining calcium-imaging experiments and in silico approaches. ggTas2r models were used to virtually screen BitterDB compounds. ~50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested with in vitro and in vivo experiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.

  • Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case
    Scientific Reports, 2017
    Co-Authors: Antonella Pizio, Louisa-marie Kruetzfeldt, Shira Cheled-shoval, Wolfgang Meyerhof, Maik Behrens, Masha Y. Niv
    Abstract:

    Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1. Because of low sequence similarity between ggTas2r1 and crystallized GPCRs (~10% identity, ~30% similarity at most), the combination of computational approaches with site-directed mutagenesis was used to characterize the agonist-bound conformation of ggTas2r1 binding site between TMs 3, 5, 6 and 7. We found that the ligand interactions with N93 in TM3 and/or N247 in TM5, combined with hydrophobic contacts, are typically involved in agonist recognition. Next, the ggTas2r1 structural model was successfully used to identify three quinine analogues (epiquinidine, Ethylhydrocupreine, quinidine) as new ggTas2r1 agonists. The integrated approach validated here may be applicable to additional cases where the sequence identity of the GPCR of interest and the existing experimental structures is low.

Maik Behrens - One of the best experts on this subject based on the ideXlab platform.

  • Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors.
    Frontiers in molecular biosciences, 2018
    Co-Authors: Antonella Pizio, Wolfgang Meyerhof, Maik Behrens, Nitzan Shy, Masha Y. Niv
    Abstract:

    Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallus taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys3.29 and Asn3.36 are suggested as ggTas2r1-specificity-conferring residues; Gln6.55 as ggTas2r2-specificity-conferring residue; Ser5.38 and Gln7.42 as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and Ethylhydrocupreine, was then characterized by combining calcium-imaging experiments and in silico approaches. ggTas2r models were used to virtually screen BitterDB compounds. ~50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested with in vitro and in vivo experiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.

  • Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case
    Scientific Reports, 2017
    Co-Authors: Antonella Pizio, Louisa-marie Kruetzfeldt, Shira Cheled-shoval, Wolfgang Meyerhof, Maik Behrens, Masha Y. Niv
    Abstract:

    Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1. Because of low sequence similarity between ggTas2r1 and crystallized GPCRs (~10% identity, ~30% similarity at most), the combination of computational approaches with site-directed mutagenesis was used to characterize the agonist-bound conformation of ggTas2r1 binding site between TMs 3, 5, 6 and 7. We found that the ligand interactions with N93 in TM3 and/or N247 in TM5, combined with hydrophobic contacts, are typically involved in agonist recognition. Next, the ggTas2r1 structural model was successfully used to identify three quinine analogues (epiquinidine, Ethylhydrocupreine, quinidine) as new ggTas2r1 agonists. The integrated approach validated here may be applicable to additional cases where the sequence identity of the GPCR of interest and the existing experimental structures is low.

Wolfgang Meyerhof - One of the best experts on this subject based on the ideXlab platform.

  • Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors.
    Frontiers in molecular biosciences, 2018
    Co-Authors: Antonella Pizio, Wolfgang Meyerhof, Maik Behrens, Nitzan Shy, Masha Y. Niv
    Abstract:

    Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallus taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys3.29 and Asn3.36 are suggested as ggTas2r1-specificity-conferring residues; Gln6.55 as ggTas2r2-specificity-conferring residue; Ser5.38 and Gln7.42 as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and Ethylhydrocupreine, was then characterized by combining calcium-imaging experiments and in silico approaches. ggTas2r models were used to virtually screen BitterDB compounds. ~50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested with in vitro and in vivo experiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.

  • Ligand binding modes from low resolution GPCR models and mutagenesis: chicken bitter taste receptor as a test-case
    Scientific Reports, 2017
    Co-Authors: Antonella Pizio, Louisa-marie Kruetzfeldt, Shira Cheled-shoval, Wolfgang Meyerhof, Maik Behrens, Masha Y. Niv
    Abstract:

    Bitter taste is one of the basic taste modalities, warning against consuming potential poisons. Bitter compounds activate members of the bitter taste receptor (Tas2r) subfamily of G protein-coupled receptors (GPCRs). The number of functional Tas2rs is species-dependent. Chickens represent an intriguing minimalistic model, because they detect the bitter taste of structurally different molecules with merely three bitter taste receptor subtypes. We investigated the binding modes of several known agonists of a representative chicken bitter taste receptor, ggTas2r1. Because of low sequence similarity between ggTas2r1 and crystallized GPCRs (~10% identity, ~30% similarity at most), the combination of computational approaches with site-directed mutagenesis was used to characterize the agonist-bound conformation of ggTas2r1 binding site between TMs 3, 5, 6 and 7. We found that the ligand interactions with N93 in TM3 and/or N247 in TM5, combined with hydrophobic contacts, are typically involved in agonist recognition. Next, the ggTas2r1 structural model was successfully used to identify three quinine analogues (epiquinidine, Ethylhydrocupreine, quinidine) as new ggTas2r1 agonists. The integrated approach validated here may be applicable to additional cases where the sequence identity of the GPCR of interest and the existing experimental structures is low.

Nitzan Shy - One of the best experts on this subject based on the ideXlab platform.

  • Molecular Features Underlying Selectivity in Chicken Bitter Taste Receptors.
    Frontiers in molecular biosciences, 2018
    Co-Authors: Antonella Pizio, Wolfgang Meyerhof, Maik Behrens, Nitzan Shy, Masha Y. Niv
    Abstract:

    Chickens sense the bitter taste of structurally different molecules with merely three bitter taste receptors (Gallus gallus taste 2 receptors, ggTas2rs), representing a minimal case of bitter perception. Some bitter compounds like quinine, diphenidol and chlorpheniramine, activate all three ggTas2rs, while others selectively activate one or two of the receptors. We focus on bitter compounds with different selectivity profiles toward the three receptors, to shed light on the molecular recognition complexity in bitter taste. Using homology modeling and induced-fit docking simulations, we investigated the binding modes of ggTas2r agonists. Interestingly, promiscuous compounds are predicted to establish polar interactions with position 6.51 and hydrophobic interactions with positions 3.32 and 5.42 in all ggTas2rs; whereas certain residues are responsible for receptor selectivity. Lys3.29 and Asn3.36 are suggested as ggTas2r1-specificity-conferring residues; Gln6.55 as ggTas2r2-specificity-conferring residue; Ser5.38 and Gln7.42 as ggTas2r7-specificity conferring residues. The selectivity profile of quinine analogs, quinidine, epiquinidine and Ethylhydrocupreine, was then characterized by combining calcium-imaging experiments and in silico approaches. ggTas2r models were used to virtually screen BitterDB compounds. ~50% of compounds known to be bitter to human are likely to be bitter to chicken, with 25, 20, 37% predicted to be ggTas2r1, ggTas2r2, ggTas2r7 agonists, respectively. Predicted ggTas2rs agonists can be tested with in vitro and in vivo experiments, contributing to our understanding of bitter taste in chicken and, consequently, to the improvement of chicken feed.