Application | Comment | Organism |
---|---|---|
drug development | validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism | Homo sapiens |
medicine | validation of GGDPS as a therapeutic target and assesses the advantages of targeting GGDPS relative to other enzymes involved in geranylgeranylation. Compounds that directly inhibit geranylgeranyl diphosphate synthesis may also display therapeutic efficacy in bone diseases, with potential to decrease side effects unrelated to the mechanism | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
4-[(5-[[4-(3-chlorophenyl)-3-oxopiperazin-1-yl]methyl]-1H-imidazol-1-yl)methyl]benzonitrile | a dual prenyl transferase inhibitor that has advanced to clinical trials | Homo sapiens | |
additional information | GGDPS inhibitors versus geranylgeranyl transferase inhibitors in cancer therapy, overview. The use of GGDPS inhibitors, thereby blocking prenylation of both sets of geranylgeranylated proteins, may be more effective than targeting either set alone through the use of a geranylgeranyl transferase I inhibitor or a geranylgeranyl transferase II inhibitor (such as the phosphonocarboxylate 3-PEHPC); statins inhibit the enzyme indirectly through feedback inhibition via inhibition of the first and rate-limiting step of isoprenoid biosynthesis, namely, conversion of HMG-CoA to mevalonate by HMG-CoA reductase. Geranylgeranyl diphosphate depletion (and consequently geranylgeranylation) is strongly linked to statin-induced apoptosis in several models. In endothelial cells, statins potentiate tumor necrosis factor-alpha-mediated apoptosis by blocking rhoA geranylgeranylation | Homo sapiens | |
N-([5-[(1H-imidazol-4-ylmethyl)amino]-2'-methylbiphenyl-2-yl]carbonyl)-L-leucine | - |
Homo sapiens | |
nitrogeneous biphosphonates | - |
Homo sapiens | |
[(6E,11E)-2,6,12,16-tetramethylheptadeca-2,6,11,15-tetraene-9,9-diyl]bis(phosphonic acid) | - |
Homo sapiens | |
[1-hydroxy-2-(1,1':4',1''-terphenyl-3-yl)ethane-1,1-diyl]bis(phosphonic acid) | - |
Homo sapiens | |
[1-hydroxy-2-(pyridin-3-yl)ethane-1,1-diyl]bis(phosphonic acid) | - |
Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
cytosol | - |
Homo sapiens | 5829 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate | Homo sapiens | - |
diphosphate + geranylgeranyl diphosphate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
lipoprotein | proteins modified post-translationally by geranylgeranylation have been implicated in numerous cellular processes related to human disease, e.g. geranylgeranylation of Rab27B is required for the formation of xenograft tumors in the breast cancer cell line MCF-7 | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
endothelial cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate | - |
Homo sapiens | diphosphate + geranylgeranyl diphosphate | - |
? |
Synonyms | Comment | Organism |
---|---|---|
GGDPS | - |
Homo sapiens |
General Information | Comment | Organism |
---|---|---|
physiological function | the primary cellular use of geranylgeranyl diphosphate in humans is post-translational incorporation into proteins, a process known as geranylgeranylation. proteins modified post-translationally by geranylgeranylation are implicated in numerous cellular processes related to human disease, e.g. geranylgeranylation of Rab27B is required for the formation of xenograft tumors in the breast cancer cell line MCF-7. Isoprenoids regulate geranylgeranyl diphosphate synthesis through several feedback mechanisms, overview | Homo sapiens |