4PIV: Human Fatty Acid Synthase Psi/KR Tri-Domain with NADPH and GSK2194069

Human fatty acid synthase (hFAS) is a complex, multifunctional enzyme that is solely responsible for the de novo synthesis of long chain fatty acids. hFAS is highly expressed in a number of cancers, with low expression observed in most normal tissues. Although normal tissues tend to obtain fatty acids from the diet, tumor tissues rely on de novo fatty acid synthesis, making hFAS an attractive metabolic target for the treatment of cancer. We describe here the identification of GSK2194069, a potent and specific inhibitor of the beta-ketoacyl reductase (KR) activity of hFAS; the characterization of its enzymatic and cellular mechanism of action; and its inhibition of human tumor cell growth. We also present the design of a new protein construct suitable for crystallography, which resulted in what is to our knowledge the first co-crystal structure of the human KR domain and includes a bound inhibitor.
PDB ID: 4PIVDownload
MMDB ID: 121739
PDB Deposition Date: 2014/5/9
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 2.299  Å
Source Organism:
Similar Structures:
Biological Unit for 4PIV: monomeric; determined by author
Molecular Components in 4PIV
Label Count Molecule
Protein (1 molecule)
Fatty Acid Synthase(Gene symbol: FASN)
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB