Crystallographic study of FABP5 as an intracellular endocannabinoid transporter. (1st February 2014)

• Record Type: Journal Article
• Authors: Sanson, Benoît; Wang, Tao; Sun, Jing; Wang, Liqun; Kaczocha, Martin; Ojima, Iwao; Deutsch, Dale; Li, Huilin
• Is Part Of: Acta crystallographica. Volume 70:Part 2(2014:Feb.)
• Page Start: 290
• Page End: 298
• Publication Date: 2014-02-01
• Subjects: Biomolecules -- Structure -- Periodicals; Physical biochemistry -- Periodicals; X-ray crystallography -- Periodicals; Crystallography -- Periodicals; 572
• DOI: 10.1107/S1399004713026795
• Languages: English
• ISSNs: 0907-4449

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>In addition to binding intracellular fatty acids, fatty‐acid‐binding proteins (FABPs) have recently been reported to also transport the endocannabinoids anandamide (AEA) and 2‐arachidonoylglycerol (2‐AG), arachidonic acid derivatives that function as neurotransmitters and mediate a diverse set of physiological and psychological processes. To understand how the endocannabinoids bind to FABPs, the crystal structures of FABP5 in complex with AEA, 2‐AG and the inhibitor BMS‐309403 were determined. These ligands are shown to interact primarily with the substrate‐binding pocket <italic>via</italic> hydrophobic interactions as well as a common hydrogen bond to the Tyr131 residue. This work advances our understanding of FABP5–endocannabinoid interactions and may be useful for future efforts in the development of small‐molecule inhibitors to raise endocannabinoid levels.</p> </abstract>