4DO3

Structure of FAAH with a non-steroidal anti-inflammatory drug

Summary for 4DO3

• Entry DOI: 10.2210/pdb4do3/pdb
• Related: 1M5T 2VYA 3LJ7
• Descriptor: Fatty-acid amide hydrolase 1, CHLORIDE ION, CYCLOHEXANE AMINOCARBOXYLIC ACID, ... (5 entities in total)
• Functional Keywords: amidase, hydrolase, anandamide, nsaid, drug, cox, inhibitor, inflammation, pain, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Rattus norvegicus (rat)
• Cellular location: Endoplasmic reticulum membrane; Single-pass membrane protein: P97612
• Total number of polymer chains: 2
• Total formula weight: 126614.04

Authors

Garau, G. (deposition date: 2012-02-09, release date: 2013-01-23, Last modification date: 2023-09-13)

Primary citation

Bertolacci, L.,Romeo, E.,Veronesi, M.,Magotti, P.,Albani, C.,Dionisi, M.,Lambruschini, C.,Scarpelli, R.,Cavalli, A.,De Vivo, M.,Piomelli, D.,Garau, G.
A Binding Site for Nonsteroidal Anti-inflammatory Drugs in Fatty Acid Amide Hydrolase.
J.Am.Chem.Soc., 135:22-25, 2013

PubMed Abstract: In addition to inhibiting the cyclooxygenase (COX)-mediated biosynthesis of prostanoids, various widely used nonsteroidal anti-inflammatory drugs (NSAIDs) enhance endocannabinoid signaling by blocking the anandamide-degrading membrane enzyme fatty acid amide hydrolase (FAAH). The X-ray structure of FAAH in complex with the NSAID carprofen, along with site-directed mutagenesis, enzyme activity assays, and NMR analysis, has revealed the molecular details of this interaction, providing information that may guide the design of dual FAAH-COX inhibitors with superior analgesic efficacy.

PubMed: 23240907
DOI: 10.1021/ja308733u

Experimental method

X-RAY DIFFRACTION (2.25 Å)