6dii

Structure of Arabidopsis Fatty Acid Amide Hydrolase in Complex with methyl linolenyl fluorophosphonate

spinqualitylabelsall models 6dii, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dii is a 12 chain structure with sequence from Arabidopsis thaliana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: GJY Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FAAH_ARATH Degrades bioactive fatty acid amides to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Converts N-actylethanolamine (NAE) to ethanolamine. Can also use oleamide or 2-arachidonylglycerol as substrates, but not indole-3-acetamide, 1-naphtalene-acetamide, nicotinic acid amide or L-asparagine. Might be involved in abscisic acid signaling and plant defense through distinctly different mechanisms not involving the catalytic activity. Publication Abstract from PubMed N-Acylethanolamines (NAEs) are fatty-acid derivatives that in animal systems include the well-known bioactive metabolites of the endocannabinoid signaling pathway. Plants use NAE signaling as well, and these bioactive molecules often have oxygenated acyl moieties. Here, we report the three-dimensional crystal structures of the signal-terminating enzyme fatty acid amide hydrolase (FAAH) from Arabidopsis in its apo and ligand-bound forms at 2.1 A and 3.2 A resolutions, respectively. This plant FAAH structure revealed features distinct from those of the only other available FAAH structure (rat). The structures disclosed that although catalytic residues are conserved with the mammalian enzyme, AtFAAH has a more open substrate-binding pocket that is partially lined with polar residues. Fundamental differences in the organization of the membrane-binding "cap" and the membrane access channel also were evident. In accordance with the observed structural features of the substrate-binding pocket, kinetic analysis showed that AtFAAH efficiently uses both unsubstituted and oxygenated acylethanolamides as substrates. Moreover, comparison of the apo and ligand-bound AtFAAH structures identified three discrete sets of conformational changes that accompany ligand binding, suggesting a unique "squeeze and lock" substrate-binding mechanism. Using molecular dynamics simulations, we evaluated these conformational changes further and noted a partial unfolding of a random-coil helix within the region 531-537 in the apo structure, but not in the ligand-bound form, indicating that this region likely confers plasticity to the substrate-binding pocket. We conclude that the structural divergence in bioactive acylethanolamides in plants is reflected in part in the structural and functional properties of plant FAAHs. Structural analysis of a plant fatty acid amide hydrolase provides insights into the evolutionary diversity of bioactive acylethanolamides.,Aziz M, Wang X, Tripathi A, Bankaitis VA, Chapman KD J Biol Chem. 2019 Mar 20. pii: RA118.006672. doi: 10.1074/jbc.RA118.006672. PMID:30894416 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Fatty acid amide hydrolase

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