› 4m6q

X-ray diffraction
2.41Å resolution

Identification of Amides Derived From 1H-Pyrazolo[3,4-b]pyridine-5-carboxylic Acid as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

Released:
DOI: 10.2210/pdb4m6q/pdb
PDB entry 4m6q coloured by chain, front view.
PDB entry 4m6q coloured by chain, side view.
PDB entry 4m6q coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT).
Zheng X, Bair KW, Bauer P, Baumeister T, Bowman KK, Buckmelter AJ, Caligiuri M, Clodfelter KH, Feng Y, Han B, Ho YC, Kley N, Li H, Liang X, Liederer BM, Lin J, Ly J, O'Brien T, Oeh J, Oh A, Reynolds DJ, Sampath D, Sharma G, Skelton N, Smith CC, Tremayne J, Wang L, Wang W, Wang Z, Wu H, Wu J, Xiao Y, Yang G, Yuen PW, Zak M, Dragovich PS
Bioorg Med Chem Lett 23 5488-97 (2013)
PMID: 24021463

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 20T 2 x 20T
Ligand POP 2 x POP
Ligand PO4 2 x PO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.2
Spacegroup: P21
Unit cell:
a: 60.355Å b: 107.016Å c: 82.844Å
α: 90° β: 96.56° γ: 90°
R-values:
R R work R free
0.175 0.173 0.22
Expression system: Escherichia coli

Quick links

Citations

5 review citations

NAD Metabolism in Cancer Therapeutics.
Yaku et al. (2018)
4 more