› 4j5p

X-ray diffraction
2.3Å resolution

Crystal Structure of a Covalently Bound alpha-Ketoheterocycle Inhibitor (Phenhexyl/Oxadiazole/Pyridine) to a Humanized Variant of Fatty Acid Amide Hydrolase

Released:
DOI: 10.2210/pdb4j5p/pdb
PDB entry 4j5p coloured by chain, front view.
PDB entry 4j5p coloured by chain, side view.
PDB entry 4j5p coloured by chain, top view.
Source organism: Rattus norvegicus
Primary publication:
Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues.
Otrubova K, Brown M, McCormick MS, Han GW, O'Neal ST, Cravatt BF, Stevens RC, Lichtman AH, Boger DL
J Am Chem Soc 135 6289-99 (2013)
PMID: 23581831

Function and Biology Details

Reaction catalysed: 
Anandamide + H(2)O = arachidonic acid + ethanolamine
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-161319 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Fatty-acid amide hydrolase 1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 573 amino acids
Theoretical weight: 63.11 KDa
Source organism: Rattus norvegicus
Expression system: Escherichia coli BL21
UniProt:
  • Canonical: P97612 (Residues: 30-579; Coverage: 95%)
Gene names: Faah, Faah1
Sequence domains: Amidase
Structure domains: Amidase signature (AS) domain

Ligands and Environments

3 bound ligands:
Ligand BR1 2 x BR1
Ligand PEG 5 x PEG
Ligand CL 1 x CL
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRL BEAMLINE BL11-1
Spacegroup: P3221
Unit cell:
a: 104.067Å b: 104.067Å c: 261.034Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.222 0.22 0.265
Expression system: Escherichia coli BL21

Quick links

Citations

2 review citations

Targeted Covalent Inhibitors for Drug Design.
Baillie TA. (2016)
1 more

1 mention without citation

Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues.
Otrubova et al. (2013)