The Experts below are selected from a list of 30 Experts worldwide ranked by ideXlab platform
Kent D. Chapman - One of the best experts on this subject based on the ideXlab platform.
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fatty acid Amide Hydrolases an expanded capacity for chemical communication
Trends in Plant Science, 2020Co-Authors: Mina Aziz, Kent D. ChapmanAbstract:Fatty acid Amide hydrolase (FAAH) is an enzyme that belongs to the amidase signature (AS) superfamily and is widely distributed in multicellular eukaryotes. FAAH hydrolyzes lipid signaling molecules – namely, N-acylethanolamines (NAEs) – which terminates their actions. Recently, the crystal structure of Arabidopsis thaliana FAAH was solved and key residues were identified for substrate-specific interactions. Here, focusing on residues surrounding the substrate-binding pocket, a comprehensive analysis of FAAH sequences from angiosperms reveals a distinctly different family of FAAH-like enzymes. We hypothesize that FAAH, in addition to its role in seedling development, also acts in an N-acyl Amide communication axis to facilitate plant–microbe interactions and that structural diversity provides for the flexible use of a wide range of small lipophilic signaling molecules.
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Lipid signaling in plants - Lipid signaling in plants.
Frontiers in Plant Science, 2013Co-Authors: Xuemin Wang, Kent D. ChapmanAbstract:Membrane lipids provide both the structural basis for cell membranes and a rich source of cellular mediators that regulate many aspects of plant development and environmental interactions. Over recent years, lipids as hormones and signaling messengers have gained increasing attention in the plant biology community. This volume collected 20 articles, including both primary research articles and several timely reviews on lipid signaling pathways, from active researchers addressing various fundamental questions in lipid signaling in plants (Ibrahim et al., 2011; Alford et al., 2012; Benning et al., 2012; Berkey et al., 2012; Dave and Graham, 2012; Dieck et al., 2012; Ge et al., 2012; Guo and Wang, 2012; Jung et al., 2012; Koo and Howe, 2012; Lorenc-Kukula et al., 2012; Maatta et al., 2012; Pleskot et al., 2012; Scherer et al., 2012; Stenzel et al., 2012; Strawn et al., 2012; Teaster et al., 2012; Wager and Browse, 2012; Xia et al., 2012; Arisz et al., 2013). One important question addressed is what lipids act as mediators in plants, and several classes of lipids and their related metabolites have been described, including phosphatidic acid, oxylipins, phosphoinositides, sphingolipids, free fatty acids, lysophospholipids, N-acylethanolamines, oxidatively modified galactolipids, and others. In addition, advances in mass spectrometry-based analysis, which allow sensitive identification of lipids with structural information, have raised many new questions: How many lipids are there in plants? How do plant lipidomes change in response to growth, developmental, and stress cues? As a result, many lipid mediators remain to be identified, and this volume provides a current, baseline knowledge on lipid signaling molecules and their actions in plants. Signaling lipids are produced and metabolized by a number of enzymes described in this volume, including phospholipase Ds, phospholipase As, acyl Hydrolases, phytosphingosine kinases, diacylglcerol kinases, fatty acid Amide Hydrolases. Each enzyme class has multiple members, which contribute to the spatial and temporal production of lipid mediators, as well as to the influence of specific molecular species for selected actions. Additional molecular complexity is afforded by the fact that each class of lipid mediators may be produced by different enzymes. Different approaches, such as genetic ablation of specific genes, enzymatic kinetics, lipid profiling, or differential metabolic labeling, have been applied. Deciphering the complexity of lipid molecular signals and their metabolism has been a challenge. Lipid signaling plays diverse roles in various cellular and physiological processes. The involvement of lipid mediators has been discussed here in plant responses to hormones (e.g., abscisic acid and auxin), abiotic stresses, plant-microbe interactions, and in plant growth and development. Some intriguing aspects of plant lipid mediators are also addressed, such as how lipids might play roles as long distance mobile signals in addition to their localized actions, contributing to processes such as flowering and defense against pathogens. One major challenge has been to elucidate mechanistically how lipid mediators carry out their functions. Recent advances in oxylipins, particularly metabolites in the jasmonate pathway, provide an excellent example of how some key players in the signaling cascade that have been identified and interact directly with target proteins to influence changes in gene transcription. At the same time, these articles on oxylipins emphasize the difficulty of assigning functions to lipid mediators when multiple metabolites within a pathway have biological actions (i.e., OPDA, jasmonate and jasmonyl-leu, and probably others). Identifying lipid-interacting proteins represents an exciting area for future research that will improve our understanding of how different signaling networks in plant cells are integrated. However, translating the milieu of lipid metabolite changes in cells into the mechanisms for regulation of physiological processes in plants will remain a formidable challenge in the coming years. Elsewhere in the volume, the contribution of lipid head-group differences and their potential for selective actions are suggested. The potential roles of phosphoinositides in nuclear function and in the dynamics of membrane trafficking and cell expansion are discussed. In addition, head-group modifications and their metabolites, like the myo-inositol phosphates, appear to play a role in energy homeostasis in plants. Furthermore, biophysical studies have provided information on how PA and its phosphorylated product, diacylglycerol pyrophosphate, interact with proteins and/or cell membranes, suggesting a means for different cellular effects of these two metabolically related classes of signaling lipids. The publication of this book would not have been possible without the efforts of many people. First and foremost are the authors who responded enthusiastically to the call to contribute to the special volume. And the essential critical comments from the many peer reviewers are gratefully acknowledged which provided valuable feedback to ensure the highest quality, and up-to-date information in the articles.
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plant fatty acid ethanol Amide Hydrolases
Biochimica et Biophysica Acta, 2006Co-Authors: Rhidaya Shrestha, John M Dyer, Richard A Dixon, Kent D. ChapmanAbstract:Fatty acid Amide hydrolase (FAAH) plays a central role in modulating endogenous N-acylethanolamine (NAE) levels in vertebrates, and, in part, constitutes an “endocannabinoid” signaling pathway that regulates diverse physiological and behavioral processes in animals. Recently, an Arabidopsis FAAH homologue was identified which catalyzed the hydrolysis of NAEs in vitro suggesting a FAAH-mediated pathway exists in plants for the metabolism of endogenous NAEs. Here, we provide evidence to support this concept by identifying candidate FAAH genes in monocots (Oryza sativa) and legumes (Medicago truncatula), which have similar, but not identical, exon–intron organizations. Corresponding M. truncatula and rice cDNAs were isolated and cloned into prokaryotic expression vectors and expressed as recombinant proteins in Escherichia coli. NAE amidohydrolase assays confirmed that these proteins indeed catalyzed the hydrolysis of 14 C-labeled NAEs in vitro. Kinetic parameters and inhibition properties of the rice FAAH were similar to those of Arabidopsis and rat FAAH, but not identical. Sequence alignments and motif analysis of plant FAAH enzymes revealed a conserved domain organization for these members of the amidase superfamily. Five amino-acid residues determined to be important for catalysis by rat FAAH were absolutely conserved within the FAAH sequences of six plant species. Homology modeling of the plant FAAH proteins using the rat FAAH crystal structure as a template revealed a conserved protein core that formed the active site of each enzyme. Collectively, these results indicate that plant and mammalian FAAH proteins have similar structure/activity relationships despite limited overall sequence identity. Defining the molecular properties of NAE amidohydrolase enzymes in plants will help to better understand the metabolic regulation of NAE lipid mediators.
Benjamin F Cravatt - One of the best experts on this subject based on the ideXlab platform.
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rat and human fatty acid Amide Hydrolases overt similarities and hidden differences
Biochimica et Biophysica Acta, 2012Co-Authors: Almerinda Di Venere, Benjamin F Cravatt, Enrico Dainese, Filomena Fezza, Beatrice Clotilde Angelucci, Nicola Rosato, Alessandro Finazziagro, Mauro MaccarroneAbstract:Abstract Fatty acid Amide hydrolase (FAAH) is a membrane protein that plays a relevant role in the metabolism of fatty acid Amides and esters. It degrades important neurotransmitters such as oleAmide and anandAmide, and it has been involved in a number of human pathological conditions, representing therefore a valuable target for biochemical and pharmacological research. In this study, we have investigated in vitro the structure–function relationship of rat and human FAAHs. In particular circular dichroism, fluorescence spectroscopy and light scattering measurements have been performed, in order to characterize the structural features of the two proteins, both in the presence and absence of the irreversible inhibitor methoxyarachidonyl-fluorophosphonate. The results demonstrate that the structural dynamics of the two FAAHs are different, despite their high sequence homology and overall similarity in temperature-dependence. Additionally, membrane binding and kinetic assays of both FAAHs indicate that also the functional properties of the two enzymes are different in their interaction with lipid bilayers and with exogenous inhibitors. These findings suggest that pre-clinical studies of FAAH-dependent human diseases based only on animal models should be interpreted with caution, and that the efficacy of new drugs targeted to FAAH should be tested in vitro, on both rat and human enzymes.
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molecular characterization of human and mouse fatty acid Amide Hydrolases
Proceedings of the National Academy of Sciences of the United States of America, 1997Co-Authors: Dan K Giang, Benjamin F CravattAbstract:Recently, we reported the isolation, cloning, and expression of a rat enzyme, fatty acid Amide hydrolase (FAAH), that degrades bioactive fatty acid Amides like oleAmide and anandAmide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Here, we report the molecular characterization of both a mouse and a human FAAH and compare these enzymes to the rat FAAH. The enzymes are well conserved in primary structure, with the mouse and rat FAAHs sharing 91% amino acid identity and the human FAAH sharing 82% and 84% identity with the rat FAAH and mouse FAAH, respectively. In addition, the expressed human and rat FAAHs behave biochemically as membrane proteins of comparable molecular size and show similar, but distinguishable, enzymological properties. The identification of highly homologous FAAH proteins in rat, mouse, and human supports a general role for the fatty acid Amides in mammalian biology.
Rhidaya Shrestha - One of the best experts on this subject based on the ideXlab platform.
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plant fatty acid ethanol Amide Hydrolases
Biochimica et Biophysica Acta, 2006Co-Authors: Rhidaya Shrestha, John M Dyer, Richard A Dixon, Kent D. ChapmanAbstract:Fatty acid Amide hydrolase (FAAH) plays a central role in modulating endogenous N-acylethanolamine (NAE) levels in vertebrates, and, in part, constitutes an “endocannabinoid” signaling pathway that regulates diverse physiological and behavioral processes in animals. Recently, an Arabidopsis FAAH homologue was identified which catalyzed the hydrolysis of NAEs in vitro suggesting a FAAH-mediated pathway exists in plants for the metabolism of endogenous NAEs. Here, we provide evidence to support this concept by identifying candidate FAAH genes in monocots (Oryza sativa) and legumes (Medicago truncatula), which have similar, but not identical, exon–intron organizations. Corresponding M. truncatula and rice cDNAs were isolated and cloned into prokaryotic expression vectors and expressed as recombinant proteins in Escherichia coli. NAE amidohydrolase assays confirmed that these proteins indeed catalyzed the hydrolysis of 14 C-labeled NAEs in vitro. Kinetic parameters and inhibition properties of the rice FAAH were similar to those of Arabidopsis and rat FAAH, but not identical. Sequence alignments and motif analysis of plant FAAH enzymes revealed a conserved domain organization for these members of the amidase superfamily. Five amino-acid residues determined to be important for catalysis by rat FAAH were absolutely conserved within the FAAH sequences of six plant species. Homology modeling of the plant FAAH proteins using the rat FAAH crystal structure as a template revealed a conserved protein core that formed the active site of each enzyme. Collectively, these results indicate that plant and mammalian FAAH proteins have similar structure/activity relationships despite limited overall sequence identity. Defining the molecular properties of NAE amidohydrolase enzymes in plants will help to better understand the metabolic regulation of NAE lipid mediators.
Richard A Dixon - One of the best experts on this subject based on the ideXlab platform.
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plant fatty acid ethanol Amide Hydrolases
Biochimica et Biophysica Acta, 2006Co-Authors: Rhidaya Shrestha, John M Dyer, Richard A Dixon, Kent D. ChapmanAbstract:Fatty acid Amide hydrolase (FAAH) plays a central role in modulating endogenous N-acylethanolamine (NAE) levels in vertebrates, and, in part, constitutes an “endocannabinoid” signaling pathway that regulates diverse physiological and behavioral processes in animals. Recently, an Arabidopsis FAAH homologue was identified which catalyzed the hydrolysis of NAEs in vitro suggesting a FAAH-mediated pathway exists in plants for the metabolism of endogenous NAEs. Here, we provide evidence to support this concept by identifying candidate FAAH genes in monocots (Oryza sativa) and legumes (Medicago truncatula), which have similar, but not identical, exon–intron organizations. Corresponding M. truncatula and rice cDNAs were isolated and cloned into prokaryotic expression vectors and expressed as recombinant proteins in Escherichia coli. NAE amidohydrolase assays confirmed that these proteins indeed catalyzed the hydrolysis of 14 C-labeled NAEs in vitro. Kinetic parameters and inhibition properties of the rice FAAH were similar to those of Arabidopsis and rat FAAH, but not identical. Sequence alignments and motif analysis of plant FAAH enzymes revealed a conserved domain organization for these members of the amidase superfamily. Five amino-acid residues determined to be important for catalysis by rat FAAH were absolutely conserved within the FAAH sequences of six plant species. Homology modeling of the plant FAAH proteins using the rat FAAH crystal structure as a template revealed a conserved protein core that formed the active site of each enzyme. Collectively, these results indicate that plant and mammalian FAAH proteins have similar structure/activity relationships despite limited overall sequence identity. Defining the molecular properties of NAE amidohydrolase enzymes in plants will help to better understand the metabolic regulation of NAE lipid mediators.
John M Dyer - One of the best experts on this subject based on the ideXlab platform.
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plant fatty acid ethanol Amide Hydrolases
Biochimica et Biophysica Acta, 2006Co-Authors: Rhidaya Shrestha, John M Dyer, Richard A Dixon, Kent D. ChapmanAbstract:Fatty acid Amide hydrolase (FAAH) plays a central role in modulating endogenous N-acylethanolamine (NAE) levels in vertebrates, and, in part, constitutes an “endocannabinoid” signaling pathway that regulates diverse physiological and behavioral processes in animals. Recently, an Arabidopsis FAAH homologue was identified which catalyzed the hydrolysis of NAEs in vitro suggesting a FAAH-mediated pathway exists in plants for the metabolism of endogenous NAEs. Here, we provide evidence to support this concept by identifying candidate FAAH genes in monocots (Oryza sativa) and legumes (Medicago truncatula), which have similar, but not identical, exon–intron organizations. Corresponding M. truncatula and rice cDNAs were isolated and cloned into prokaryotic expression vectors and expressed as recombinant proteins in Escherichia coli. NAE amidohydrolase assays confirmed that these proteins indeed catalyzed the hydrolysis of 14 C-labeled NAEs in vitro. Kinetic parameters and inhibition properties of the rice FAAH were similar to those of Arabidopsis and rat FAAH, but not identical. Sequence alignments and motif analysis of plant FAAH enzymes revealed a conserved domain organization for these members of the amidase superfamily. Five amino-acid residues determined to be important for catalysis by rat FAAH were absolutely conserved within the FAAH sequences of six plant species. Homology modeling of the plant FAAH proteins using the rat FAAH crystal structure as a template revealed a conserved protein core that formed the active site of each enzyme. Collectively, these results indicate that plant and mammalian FAAH proteins have similar structure/activity relationships despite limited overall sequence identity. Defining the molecular properties of NAE amidohydrolase enzymes in plants will help to better understand the metabolic regulation of NAE lipid mediators.
