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Literature summary for 2.5.1.29 extracted from

  • Wiemer, A.J.; Wiemer, D.F.; Hohl, R.J.
    Geranylgeranyl diphosphate synthase: an emerging therapeutic target (2011), Clin. Pharmacol. Ther., 90, 804-812.
    View publication on PubMed

Application

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

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

Localization Comment Organism GeneOntology No. Textmining
cytosol
-
Homo sapiens 5829
-

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

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

Source Tissue Comment Organism Textmining
endothelial cell
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate
-
Homo sapiens diphosphate + geranylgeranyl diphosphate
-
?

Synonyms

Synonyms Comment Organism
GGDPS
-
Homo sapiens

General Information

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