› 4kfn

X-ray diffraction
1.6Å resolution

Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors

Released:
DOI: 10.2210/pdb4kfn/pdb
PDB entry 4kfn coloured by chain, front view.
PDB entry 4kfn coloured by chain, side view.
PDB entry 4kfn coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-based identification of ureas as novel nicotinamide phosphoribosyltransferase (Nampt) inhibitors.
Zheng X, Bauer P, Baumeister T, Buckmelter AJ, Caligiuri M, Clodfelter KH, Han B, Ho YC, Kley N, Lin J, Reynolds DJ, Sharma G, Smith CC, Wang Z, Dragovich PS, Oh A, Wang W, Zak M, Gunzner-Toste J, Zhao G, Yuen PW, Bair KW
J Med Chem 56 4921-37 (2013)
PMID: 23617784

Function and Biology Details

Reaction catalysed: 
Nicotinamide D-ribonucleotide + diphosphate = nicotinamide + 5-phospho-alpha-D-ribose 1-diphosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-155082 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Nicotinamide phosphoribosyltransferase Chains: A, B
Molecule details ›
Chains: A, B
Length: 501 amino acids
Theoretical weight: 56.94 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P43490 (Residues: 1-491; Coverage: 100%)
Gene names: NAMPT, PBEF, PBEF1
Sequence domains:
Structure domains: Aldolase class I

Ligands and Environments

3 bound ligands:
Ligand 1QR 2 x 1QR
Ligand PO4 6 x PO4
Ligand EDO 10 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P21
Unit cell:
a: 60.475Å b: 106.601Å c: 83.001Å
α: 90° β: 96.68° γ: 90°
R-values:
R R work R free
0.157 0.156 0.183
Expression system: Escherichia coli

Quick links

Citations

3 review citations

The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design.
Ling et al. (2021)
2 more

1 mention without citation

Molecular insights into the interaction between human nicotinamide phosphoribosyltransferase and Toll-like receptor 4.
Gasparrini et al. (2022)