3QK5

Crystal structure of fatty acid amide hydrolase with small molecule inhibitor

Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.186 

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Ligand Structure Quality Assessment 


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


Literature

Identification of potent, noncovalent fatty acid amide hydrolase (FAAH) inhibitors.

Gustin, D.J., Ma, Z., Min, X., Li, Y., Hedberg, C., Guimaraes, C., Porter, A.C., Lindstrom, M., Lester-Zeiner, D., Xu, G., Carlson, T.J., Xiao, S., Meleza, C., Connors, R., Wang, Z., Kayser, F.

(2011) Bioorg Med Chem Lett 21: 2492-2496

  • DOI: https://doi.org/10.1016/j.bmcl.2011.02.052
  • Primary Citation of Related Structures:  
    3QK5

  • PubMed Abstract: 

    Starting from a series of ureas that were determined to be mechanism-based inhibitors of FAAH, several spirocyclic ureas and lactams were designed and synthesized. These efforts identified a series of novel, noncovalent FAAH inhibitors with in vitro potency comparable to known covalent FAAH inhibitors. The mechanism of action for these compounds was determined through a combination of SAR and co-crystallography with rat FAAH.

    • Organizational Affiliation: 

    Department of Chemistry, Amgen Inc., South San Francisco, 1120 Veterans Blvd., South San Francisco, CA 94080, USA. dgustin@amgen.com


Macromolecules
Find similar proteins by: 
(by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Fatty-acid amide hydrolase 1
A, B
587Rattus norvegicusMutation(s): 0 
Gene Names: Faah, Faah1
EC: 3.5.1.99
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
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
QK5
Query on QK5
Download Ideal Coordinates CCD File 
C [auth A],
K [auth B]		(3-{(3R)-1-[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]piperidin-3-yl}-2-methyl-1H-pyrrolo[2,3-b]pyridin-1-yl)acetonitrile
C27 H24 N6 S
OZRJTNXVIRAQAD-FQEVSTJZSA-N
GOL
Query on GOL
Download Ideal Coordinates CCD File 
G [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
EDO
Query on EDO
Download Ideal Coordinates CCD File 
D [auth A]
E [auth A]
F [auth A]
H [auth A]
I [auth A]
D [auth A],
E [auth A],
F [auth A],
H [auth A],
I [auth A],
J [auth A],
L [auth B],
M [auth B],
N [auth B],
O [auth B],
P [auth B],
Q [auth B],
R [auth B],
S [auth B],
T [auth B]
1,2-ETHANEDIOL
C2 H6 O2
LYCAIKOWRPUZTN-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
QK5 Binding MOAD:  3QK5 IC50: 18 (nM) from 1 assay(s)
PDBBind:  3QK5 IC50: 18 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.186 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 91.431α = 90
b = 104.701β = 90
c = 148.596γ = 90
Software Package:
Software NamePurpose
MOSFLMdata reduction
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
ADSCdata collection
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-06
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description