4AZR

Human epidermal fatty acid-binding protein (FABP5) in complex with the endocannabinoid anandamide

Summary for 4AZR

• Entry DOI: 10.2210/pdb4azr/pdb
• Related: 1B56 1JJJ 4AZM 4AZN 4AZO 4AZP 4AZQ
• Descriptor: FATTY ACID-BINDING PROTEIN, EPIDERMAL, N-(2-hydroxyethyl)icosanamide, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: lipid binding protein, lipid carrier protein, beta-barrel, beta-clamshell, domain swapping
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: Q01469
• Total number of polymer chains: 2
• Total formula weight: 31654.06

Authors

Sanson, B.,Wang, T.,Sun, J.,Kaczocha, M.,Ojima, I.,Deutsch, D.,Li, H. (deposition date: 2012-06-26, release date: 2013-08-07, Last modification date: 2023-12-20)

Primary citation

Sanson, B.,Wang, T.,Sun, J.,Wang, L.,Kaczocha, M.,Ojima, I.,Deutsch, D.,Li, H.
Crystallographic Study of Fabp5 as an Intracellular Endocannabinoid Transporter.
Acta Crystallogr.,Sect.D, 70:290-, 2014

PubMed Abstract: 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 via 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.

PubMed: 24531463
DOI: 10.1107/S1399004713026795

Experimental method

X-RAY DIFFRACTION (2.95 Å)