4DO3 | pdb_00004do3

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

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 
    0.199 (Depositor), 0.200 (DCC) 
  • R-Value Work: 
    0.164 (Depositor), 0.160 (DCC) 
  • R-Value Observed: 
    0.166 (Depositor) 

Starting Model: experimental
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Ligand Structure Quality Assessment 

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This is version 1.2 of the entry. See complete history. 


Literature

A Binding Site for Nonsteroidal Anti-inflammatory Drugs in Fatty Acid Amide Hydrolase.

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.

(2013) J Am Chem Soc 135: 22-25

  • DOI: https://doi.org/10.1021/ja308733u
  • Primary Citation of Related Structures:  
    4DO3

  • 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.

    • Organizational Affiliation: 

    Drug Discovery and Development, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy.


Macromolecules
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(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fatty-acid amide hydrolase 1
A, B
571Rattus norvegicusMutation(s): 0 
Gene Names: Faah, Faah1
EC: 3.5.1.99 (PDB Primary Data), 3.1.1 (UniProt)
UniProt
Find proteins for P97612 (Rattus norvegicus)
Explore P97612 
Go to UniProtKB:  P97612
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP97612
Sequence Annotations
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
0LA BindingDB:  4DO3 IC50: min: 3.20e+4, max: 7.86e+4 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free:  0.199 (Depositor), 0.200 (DCC) 
  • R-Value Work:  0.164 (Depositor), 0.160 (DCC) 
  • R-Value Observed: 0.166 (Depositor) 
Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 103.47α = 90
b = 104.37β = 90
c = 147.62γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
MOLREPphasing
REFMACrefinement
SCALAdata scaling

Structure Validation

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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted 0LAClick on this verticalbar to view details

View more in-depth experimental data
Entry History 

Deposition Data

  • Released Date: 2013-01-23 
    • Deposition Author(s): Garau, G.

Revision History  (Full details and data files)

  • Version 1.0: 2013-01-23
    Type: Initial release
  • Version 1.1: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.2: 2024-11-06
    Changes: Structure summary