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Keys to Lipid Selection in Fatty Acid Amide Hydrolase Catalysis: Structural Flexibility, Gating Residues and Multiple Binding Pockets

Publications associées (33)

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Article Structure and functionality of a multimeric human COQ7:COQ9 complex

Matteo Dal Peraro, Luciano Andres Abriata

Coenzyme Q (CoQ) is a redox-active lipid essential for core metabolic pathways and antioxidant defense. CoQ is synthesized upon the mitochondrial inner membrane by an ill-defined "complex Q" metabolon. Here, we present structure-function analyses of a lipi ...

CELL PRESS2022

Recent evidence suggests that circadian clocks ensure temporal orchestration of lipid homeostasis and play a role in pathophysiology of metabolic diseases in humans, including type 2 diabetes (T2D). Nevertheless, circadian regulation of lipid metabolism in ...

PUBLIC LIBRARY SCIENCE2022

Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that regulate lipid biosynthesis and adipogenesis by controlling the expression of several enzymes required for cholesterol, fatty acid, triacylglycerol and phospholi ...

Springer2019

Identification of the enzymes responsible for diverse phenotypic states of yeast lipid metabolism using comprehensive mechanistic models

Sofia Tsouka

Lipids carry an important role in cell structure and function, as well as in the physiopathology of multiple diseases. Maintenance of the lipid profiles should be tightly regulated for preserving membrane permeability, cell integrity and several other func ...

2018

Mapping the diverse phenotypic states of yeast lipid metabolism to enzymes using mechanistic kinetic models

Sofia Tsouka

Lipids carry a very important role in cell structure and function, as well as in the physiopathology of many diseases. Maintenance of the lipid profiles should be tightly regulated as it is very important for preserving membrane permeability, cell integrit ...

2018

Hv1 is a transmembrane four-helix bundle that transports protons in a voltage-controlled manner. Its crucial role in many pathological conditions, including cancer and ischemic brain damage, makes Hv1 a promising drug target. Starting from the recently sol ...

Natl Acad Sciences2016

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The function of membrane proteins is best understood if their structure in the lipid membrane is known. Here, we determined the structure of the mouse serotonin 5-HT3 receptor inserted in lipid bilayers to a resolution of 12 Å without stabilizing antibodie ...

Elsevier2016

The design of multitarget-directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) ...

Wiley-V C H Verlag Gmbh2016

Computational insights into function and inhibition of fatty acid amide hydrolase

Ursula Röthlisberger, Andrea Cavalli, Giulia Palermo

The Fatty Acid Amide Hydrolase (FAAH) enzyme is a membrane-bound serine hydrolase responsible for the deactivating hydrolysis of a family of naturally occurring fatty acid amides. FAAH is a critical enzyme of the endocannabinoid system, being mainly respon ...

Elsevier2015

Anandamide Hydrolysis in FAAH Reveals a Dual Strategy for Efficient Enzyme-Assisted Amide Bond Cleavage via Nitrogen Inversion

Ursula Röthlisberger, Andrea Cavalli, Pablo Campomanes Ramos, Giulia Palermo

Herein, we combined classical molecular dynamics (MD) and quantum mechanical/molecular mechanics (QM/MM) simulations to unravel the whole catalytic cycle of fatty acid amide hydrolase (FAAH) in complex with anandamide, the main neurotransmitters involved i ...

2015