Structural Adaptations in a Membrane Enzyme That Terminates Endocannabinoid Signaling

@article{Bracey2002StructuralAI,
  title={Structural Adaptations in a Membrane Enzyme That Terminates Endocannabinoid Signaling},
  author={Michael H. Bracey and Michael A. Hanson and Kim Masuda and Raymond C. Stevens and Benjamin F. Cravatt},
  journal={Science},
  year={2002},
  volume={298},
  pages={1793 - 1796}
}
Cellular communication in the nervous system is mediated by chemical messengers that include amino acids, monoamines, peptide hormones, and lipids. An interesting question is how neurons regulate signals that are transmitted by membrane-embedded lipids. Here, we report the 2.8 angstrom crystal structure of the integral membrane protein fatty acid amide hydrolase (FAAH), an enzyme that degrades members of the endocannabinoid class of signaling lipids and terminates their activity. The structure… 
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463 Citations
Highly Influential Citations
31
Background Citations
131
Methods Citations
31
Results Citations
4

463 Citations

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Citation Type

Membrane lipids are key modulators of the endocannabinoid-hydrolase FAAH.
TLDR
It is reported that the FAAH dimer is stabilized by the lipid bilayer and shows a higher membrane-binding affinity and enzymatic activity within membranes containing both cholesterol and the natural FAAH substrate AEA (anandamide).
Fatty Acid Amide Hydrolases: An Expanded Capacity for Chemical Communication?
Structure and function of fatty acid amide hydrolase.
TLDR
Investigations into the structure and function of FAAH have engendered provocative molecular models to explain how this enzyme integrates into cell membranes and terminates fatty acid amide signaling in vivo, as well as their biological and therapeutic implications.
Fatty Acid Amide Hydrolase: From Characterization to Therapeutics
TLDR
Investigations into the structure and function of FAAH, its biological and therapeutic implications, as well as a description of different families of FAAh inhibitors are the topic of this review.
Structural analysis of a plant fatty acid amide hydrolase provides insights into the evolutionary diversity of bioactive acylethanolamides
TLDR
The structural divergence in bioactive acylethanolamides in plants is reflected in part in the structural and functional properties of plant FAAHs, suggesting a unique “squeeze and lock” substrate-binding mechanism.
Endocannabinoid biosynthesis and inactivation, from simple to complex.
The anandamide membrane transporter and the therapeutic implications of its inhibition
TLDR
Evidence in favor or against the existence of a true anandamide membrane transporter (AMT) is reviewed and the structural properties of compounds that inhibit AMT without affecting other proteins of the endocannabinoid system, such as cannabinoid receptors or FAAH are discussed.
Fatty Acid Amide Hydrolase and the Metabolism of N-Acylethanolamine Lipid Mediators in Plants
TLDR
The inactivation of NAEs is accomplished by an enzyme identified as a functional homolog of the fatty acid amide hydrolase (FAAH) that regulates endocannabinoid metabolism in vertebrates, and its role in NAE metabolism in plants is reviewed.
Occurrence, metabolism, and prospective functions of N-acylethanolamines in plants.
Structure and Dynamics of the Acyl Chains in the Membrane Trafficking and Enzymatic Processing of Lipids.
TLDR
By using molecular simulations to investigate lipid plasticity and substrate flexibility, researchers can enrich their interpretation of experimental results about the structure-function relationships of lipids and ultimately support protein engineering studies and structure-based drug discovery to target lipid-processing enzymes.
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