Farnesyl Diphosphate Synthase (FDPS)

Z-farnesyl diphosphate synthase (FDPS) is an enzyme belonging to the family of transferases, specifically those transferring aryl or alkyl groups other than methyl groups. Z-farnesyl diphosphate synthase (FDPS) functions as key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate, a precurcor for several classes of essential metabolites. FDPS catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Functions of FDPS may be inactivated by interferon-induced RSAD2. This inactivation may result of disruption of lipid rafts at the plasma membrane, and thus have an antiviral effect since many enveloped viruses need lipid rafts to bud efficiently out of the cell.

Farnesyl Diphosphate Synthase (FDPS) Related Areas

Enzyme>>Other>> FDPS

Farnesyl Diphosphate Synthase (FDPS) Alternative Names

FPPS, FPS, (2E,6E)-farnesyl diphosphate synthase; FPP synthase; FPP synthetase; dimethylallyltranstransferase; farnesyl pyrophosphate synthase; farnesyl pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase; geranyltranstransferase [Homo sapiens]

Summaries for Farnesyl Diphosphate Synthase (FDPS)

Entrez Gene summary for FDPS:

This FDPS gene encodes an enzyme that catalyzes the production of geranyl pyrophosphate and farnesyl pyrophosphate from isopentenyl pyrophosphate and dimethylallyl pyrophosphate. The resulting product, farnesyl pyrophosphate, is a key intermediate in cholesterol and sterol biosynthesis, a substrate for protein farnesylation and geranylgeranylation, and a ligand or agonist for certain hormone receptors and growth receptors. Drugs that inhibit this FDPS enzyme prevent the post-translational modifications of small GTPases and have been used to treat diseases related to bone resorption. Multiple pseudogenes have been found on chromosomes 1, 7, 14, 15, 21 and X. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2008]

OMIM - description for FDPS:

The isoprene biosynthetic pathway provides the cell with cholesterol, ubiquinone, dolichol, and other nonsterol metabolites. Farnesylpyrophosphate synthetase (EC 2.5.1.10) catalyzes the formation of both geranyl and farnesylpyrophosphate from isopentenylpyrophosphate and dimethylallyl pyrophosphate.

Human Farnesyl Diphosphate Synthase (FDPS) Protein General Information

 

• Protein names: Farnesyl pyrophosphate synthase, Short name=FPP synthase
• Sequence length: 419 AA.
• Catalytic activity: Dimethylallyl diphosphate + isopentenyl diphosphate = diphosphate + geranyl diphosphate.
  Geranyl diphosphate + isopentenyl diphosphate = diphosphate + (2E,6E)-farnesyl diphosphate.
• Cofactor: FDPS binds 3 magnesium ions per subunit.
• Enzyme regulation: FDPS is inactivated by interferon-induced RSAD2. This inactivation may result of disruption of lipid rafts at the plasma membrane, and thus have an antiviral effect since many enveloped viruses need lipid rafts to bud efficiently out of the cell.
• Sequence similarities: FDPS belongs to the FPP/GGPP synthase family.
• Pathway: Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis; farnesyl diphosphate from geranyl diphosphate and isopentenyl diphosphate: step 1/1.
  Isoprenoid biosynthesis; geranyl diphosphate biosynthesis; geranyl diphosphate from dimethylallyl diphosphate and isopentenyl diphosphate: step 1/1.
• Subunit structure: Homodimer. Interacts with RSAD2. Interacts with HTLV-1 protein p13(II).
• Subcellular location: Cytoplasm.
• Caution: It is uncertain whether Met-1 or Met-67 is the initiator.
• Sequence caution: The sequence AAA52423.1 differs from that shown. Reason: Erroneous initiation.
  The sequence BAA03523.2 differs from that shown. Reason: Erroneous initiation.

General information above from UniProt

Function for Farnesyl Diphosphate Synthase (FDPS) Protein

UniProtKB:

Farnesyl Diphosphate Synthase (FDPS) is key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. FDPS catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate.

Genatlas:

• FDPS catalyses the formation of a key cellular intermediate in isoprenoid metabolic pathways (Reilly 2002)
• FDPS also plays a role in fibroblast growth factor (FGF)-mediated signaling, and may function as a modulator of the cellular response to FGF treatment (Reilly 2002)
• FDPS is key enzyme in the isoprenoid pathway responsible for cholesterol biosynthesis, post-translational protein modifications and synthesis of steroid hormones (Romanelli 2009)

Drugs for Farnesyl Diphosphate Synthase (FDPS)

Target	Drug Name	Disease	Drug Status
FDPS	Alendronate	Osteoporosis and Paget's disease	Approved
FDPS	Risedronate	Paget's disease	Approved
FDPS	Pamidronate	Hypercalcemia	Approved
FDPS	Ibandronate	Osteoporosis in post-menopausal women	Approved
FDPS	Zoledronate	Hypercalcemia	Approved
FDPS	Pamidronate disodium	Osteoporosis	Approved
FDPS	Zoledronic acid	Postmenopausal osteoporosis	Approved

Drugs for FDPS from TTD (Therapeutic Targets Database)