› 4lvf

X-ray diffraction
1.5Å resolution

Fragment-based Identification of Amides Derived From trans-2-(Pyridin-3-yl)cyclopropanecarboxylic Acid as Potent Inhibitors of Human Nicotinamide Phosphoribosyltransferase (NAMPT)

Released:
DOI: 10.2210/pdb4lvf/pdb
PDB entry 4lvf coloured by chain, front view.
PDB entry 4lvf coloured by chain, side view.
PDB entry 4lvf 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 20P 2 x 20P
Ligand PO4 2 x PO4
Ligand EDO 16 x EDO
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U
Spacegroup: P21
Unit cell:
a: 60.528Å b: 106.999Å c: 82.964Å
α: 90° β: 96.63° γ: 90°
R-values:
R R work R free
0.172 0.135 0.172
Expression system: Escherichia coli

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Citations

5 review citations

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

2 mentions without citation

Identification of Novel Regulatory Genes in APAP Induced Hepatocyte Toxicity by a Genome-Wide CRISPR-Cas9 Screen.
Shortt et al. (2019)
1 more