› 3n45

X-ray diffraction
1.88Å resolution

Human FPPS complex with FBS_04 and zoledronic acid/MG2+

Released:
DOI: 10.2210/pdb3n45/pdb
PDB entry 3n45 coloured by chain, front view.
PDB entry 3n45 coloured by chain, side view.
PDB entry 3n45 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Allosteric non-bisphosphonate FPPS inhibitors identified by fragment-based discovery.
Jahnke W, Rondeau JM, Cotesta S, Marzinzik A, Pellé X, Geiser M, Strauss A, Götte M, Bitsch F, Hemmig R, Henry C, Lehmann S, Glickman JF, Roddy TP, Stout SJ, Green JR
Nat Chem Biol 6 660-6 (2010)
PMID: 20711197

Function and Biology Details

Reactions catalysed: 
Prenyl diphosphate + isopentenyl diphosphate = diphosphate + geranyl diphosphate
Geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2E,6E)-farnesyl diphosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-146902 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Farnesyl pyrophosphate synthase Chain: F
Molecule details ›
Chain: F
Length: 350 amino acids
Theoretical weight: 40.18 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P14324 (Residues: 72-419; Coverage: 83%)
Gene names: FDPS, FPS, KIAA1293
Sequence domains: Polyprenyl synthetase
Structure domains: Farnesyl Diphosphate Synthase

Ligands and Environments

4 bound ligands:
Ligand 3N3 1 x 3N3
Ligand ZOL 1 x ZOL
Ligand MG 3 x MG
Ligand PO4 2 x PO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X06SA
Spacegroup: P41212
Unit cell:
a: 110.753Å b: 110.753Å c: 67.966Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.198 0.196 0.225
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

25 review citations

Biochemical and molecular mechanisms of action of bisphosphonates.
Rogers et al. (2011)
24 more

3 mentions without citation

Ternary complex structures of human farnesyl pyrophosphate synthase bound with a novel inhibitor and secondary ligands provide insights into the molecular details of the enzyme's active site closure.
Park et al. (2012)
2 more