› 4n9e

X-ray diffraction
1.72Å resolution

Fragment-based Design of 3-Aminopyridine-derived Amides as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

Released:
DOI: 10.2210/pdb4n9e/pdb
PDB entry 4n9e coloured by chain, front view.
PDB entry 4n9e coloured by chain, side view.
PDB entry 4n9e coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).
Dragovich PS, Zhao G, Baumeister T, Bravo B, Giannetti AM, Ho YC, Hua R, Li G, Liang X, Ma X, O'Brien T, Oh A, Skelton NJ, Wang C, Wang W, Wang Y, Xiao Y, Yuen PW, Zak M, Zhao Q, Zheng X
Bioorg Med Chem Lett 24 954-62 (2014)
PMID: 24433859

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

4 bound ligands:
Ligand 2HL 2 x 2HL
Ligand PO4 2 x PO4
Ligand EDO 20 x EDO
Ligand DTT 2 x DTT
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 21-ID-D
Spacegroup: P21
Unit cell:
a: 60.459Å b: 106.401Å c: 83.092Å
α: 90° β: 96.52° γ: 90°
R-values:
R R work R free
0.155 0.154 0.189
Expression system: Escherichia coli

Quick links

Citations

1 review citation

From Rate-Limiting Enzyme to Therapeutic Target: The Promise of NAMPT in Neurodegenerative Diseases.
Zhu et al. (2022)
6 other articles