› 6c57

X-ray diffraction
3.5Å resolution

Crystal structure of mutant human geranylgeranyl pyrophosphate synthase (Y246D) in complex with bisphosphonate inhibitor FV0109

Released:
DOI: 10.2210/pdb6c57/pdb
PDB entry 6c57 coloured by chain, front view.
PDB entry 6c57 coloured by chain, side view.
PDB entry 6c57 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Unraveling the Prenylation-Cancer Paradox in Multiple Myeloma with Novel Geranylgeranyl Pyrophosphate Synthase (GGPPS) Inhibitors.
Lacbay CM, Waller DD, Park J, Gómez Palou M, Vincent F, Huang XF, Ta V, Berghuis AM, Sebag M, Tsantrizos YS
J Med Chem 61 6904-6917 (2018)
PMID: 30016091

Function and Biology Details

Reactions catalysed: 
Prenyl diphosphate + isopentenyl diphosphate = diphosphate + geranyl diphosphate
Geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2E,6E)-farnesyl diphosphate
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = diphosphate + geranylgeranyl diphosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-132010 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Geranylgeranyl pyrophosphate synthase Chains: A, B
Molecule details ›
Chains: A, B
Length: 322 amino acids
Theoretical weight: 37.43 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: O95749 (Residues: 1-300; Coverage: 100%)
Gene name: GGPS1
Sequence domains: Polyprenyl synthetase
Structure domains: Farnesyl Diphosphate Synthase

Ligands and Environments

1 bound ligand:
Ligand FV9 1 x FV9
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: CLSI BEAMLINE 08ID-1
Spacegroup: I422
Unit cell:
a: 185.45Å b: 185.45Å c: 114.2Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.201 0.198 0.252
Expression system: Escherichia coli

Quick links

Citations

8 review citations

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.
Gendaszewska-Darmach et al. (2021)
7 more

1 mention without citation

Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy.
Pham et al. (2024)