GGPS1 Human
Description
Molecular Function and Biochemical Role
GGPS1 catalyzes the sequential condensation of isopentenyl pyrophosphate (IPP) with farnesyl pyrophosphate (FPP) to produce GGPP . This reaction is vital for:
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Protein geranylgeranylation: Post-translational modification of small GTPases (e.g., Rho, Rac), enabling membrane localization and function in cytoskeletal regulation and signal transduction .
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Metabolic precursors: GGPP serves as a substrate for vitamin K2, ubiquinone (coenzyme Q10), and dolichol biosynthesis .
Key Enzymatic Properties
| Property | Human GGPS1 |
|---|---|
| Gene location | Chromosome 1 (1q32.1) |
| Protein length | 300 amino acids |
| Molecular mass | ~34.8 kDa |
| Quaternary structure | Hexameric assembly |
| Inhibitors | Bisphosphonates (e.g., zoledronate) |
Comparative Quaternary Structures
| Organism | Structure | Functional Implications |
|---|---|---|
| Human | Hexamer | Enhanced stability and regulation |
| E. coli | Dimer | Simpler catalytic activity |
| Archaeoglobus | Dimer | Limited regulatory capacity |
Clinical and Disease Associations
Mutations in GGPS1 are linked to rare genetic disorders and metabolic dysregulation:
Genetic Disorders
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Muscular dystrophy with hearing loss and ovarian insufficiency: Biallelic mutations (e.g., R261H, F257C) disrupt GGPP synthesis, impairing protein prenylation and cellular homeostasis .
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Perrault syndrome 2: A syndromic form of ovarian dysgenesis and sensorineural hearing loss .
Cancer and Metabolic Diseases
Therapeutic Targeting
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Bisphosphonates: Inhibit GGPS1 activity, reducing GGPP-dependent protein prenylation in bone disorders and cancers .
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Gene knockout studies: GGPS1 deficiency attenuates sepsis-induced lung injury and cancer metastasis in preclinical models .
Metabolic Pathways
GGPS1 intersects with critical pathways:
Protein Conservation Across Species
GGPS1 is highly conserved, with homologs in mammals, insects, and plants:
Future Directions
Current research focuses on:
Product Specs
GLMQLFSDYK EDLKPLLNTL GLFFQIRDDY ANLHSKEYSE NKSFCEDLTE GKFSFPTIHA IWSRPESTQV QNILRQRTEN IDIKKYCVHY LEDVGSFEYT RNTLKELEAK AYKQIDARGG NPELVALVKH LSKMFKEENE.
Product Science Overview
GGPS1 catalyzes the trans-addition of three molecules of isopentenyl pyrophosphate (IPP) onto dimethylallyl pyrophosphate (DMAPP) to form GGPP . GGPP is a key precursor for the C20-prenylation of proteins, which is essential for the post-translational modification of proteins, including those in the Ras superfamily of small GTPases . These modifications are critical for the proper functioning of various cellular processes, including signal transduction, cell growth, and differentiation .
The GGPS1 gene is located on chromosome 1q42.3 . It encodes a protein that consists of 300 amino acids and contains five conserved domains typical of prenyltransferases . The enzyme is ubiquitously expressed in various tissues, with the highest expression observed in the heart, skeletal muscle, and testis .
Mutations or dysregulation of the GGPS1 gene have been associated with several diseases, including muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome . The enzyme’s role in the mevalonate/isoprenoid pathway also implicates it in the regulation of lipid synthesis and small GTPase activity, which are fundamental to numerous cellular functions .
