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Target not currently curated in GtoImmuPdb
Target id: 643
Nomenclature: geranylgeranyl diphosphate synthase
Family: Lanosterol biosynthesis pathway
Gene and Protein Information | ||||||
Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
Human | - | 300 | 1q42.3 | GGPS1 | geranylgeranyl diphosphate synthase 1 | 1,13 |
Mouse | - | 300 | 13 5.29 cM | Ggps1 | geranylgeranyl diphosphate synthase 1 | |
Rat | - | 300 | 17q12.1 | Ggps1 | geranylgeranyl diphosphate synthase 1 |
Database Links | |
Alphafold | O95749 (Hs), Q9WTN0 (Mm), Q6F596 (Rn) |
BRENDA | 2.5.1.1, 2.5.1.10, 2.5.1.29 |
CATH/Gene3D | 1.10.600.10 |
ChEMBL Target | CHEMBL4769 (Hs) |
DrugBank Target | O95749 (Hs) |
Ensembl Gene | ENSG00000152904 (Hs), ENSMUSG00000021302 (Mm), ENSRNOG00000016767 (Rn) |
Entrez Gene | 9453 (Hs), 14593 (Mm), 291211 (Rn) |
Human Protein Atlas | ENSG00000152904 (Hs) |
KEGG Enzyme | 2.5.1.1, 2.5.1.10, 2.5.1.29 |
KEGG Gene | hsa:9453 (Hs), mmu:14593 (Mm), rno:291211 (Rn) |
OMIM | 606982 (Hs) |
Pharos | O95749 (Hs) |
RefSeq Nucleotide | NM_001037277 (Hs), NM_010282 (Mm), NM_001007626 (Rn) |
RefSeq Protein | NP_001032354 (Hs), NP_034412 (Mm), NP_001007627 (Rn) |
SynPHARM | 7185 (in complex with geranylgeranyl diphosphate) |
UniProtKB | O95749 (Hs), Q9WTN0 (Mm), Q6F596 (Rn) |
Wikipedia | GGPS1 (Hs) |
Selected 3D Structures | |||||||||||||
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Enzyme Reaction | ||||||||||||
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Substrates and Reaction Kinetics | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Cofactors | ||||||||||||||||
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Download all structure-activity data for this target as a CSV file
Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Some of the inhibitors above have been selected as representative structures from sets of stucturally similar compounds with bioactivity data at this target on ChEMBLdb.
Click here for a summary of the ChEMBL bioactivity data
Tissue Distribution | ||||||||||
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General Comments |
Geranylgeranyl diphosphate synthase has two binding sites, one binding substrate geranyl diphosphate and the other trans,trans-farnesyl diphosphate. This is reflective of its dual functionality and multiple EC number allocation [4]. |
1. Ericsson J, Greene JM, Carter KC, Shell BK, Duan DR, Florence C, Edwards PA. (1998) Human geranylgeranyl diphosphate synthase: isolation of the cDNA, chromosomal mapping and tissue expression. J Lipid Res, 39 (9): 1731-9. [PMID:9741684]
2. Ericsson J, Runquist M, Thelin A, Andersson M, Chojnacki T, Dallner G. (1993) Distribution of prenyltransferases in rat tissues. Evidence for a cytosolic all-trans-geranylgeranyl diphosphate synthase. J Biol Chem, 268 (2): 832-8. [PMID:8419360]
3. Guo RT, Cao R, Liang PH, Ko TP, Chang TH, Hudock MP, Jeng WY, Chen CK, Zhang Y, Song Y et al.. (2007) Bisphosphonates target multiple sites in both cis- and trans-prenyltransferases. Proc Natl Acad Sci USA, 104 (24): 10022-7. [PMID:17535895]
4. K-M Chen C, Hudock MP, Zhang Y, Guo RT, Cao R, No JH, Liang PH, Ko TP, Chang TH, Chang SC et al.. (2008) Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates: a crystallographic and computational investigation. J Med Chem, 51 (18): 5594-607. [PMID:18800762]
5. Kavanagh KL, Dunford JE, Bunkoczi G, Russell RG, Oppermann U. (2006) The crystal structure of human geranylgeranyl pyrophosphate synthase reveals a novel hexameric arrangement and inhibitory product binding. J Biol Chem, 281 (31): 22004-12. [PMID:16698791]
6. Matsumura Y, Kidokoro T, Miyagi Y, Marilingaiah NR, Sagami H. (2007) The carboxyl-terminal region of the geranylgeranyl diphosphate synthase is indispensable for the stabilization of the region involved in substrate binding and catalysis. J Biochem, 142 (4): 533-7. [PMID:17846065]
7. Matsumura Y, Kuzuguchi T, Sagami H. (2004) Relationship between intron 4b splicing of the rat geranylgeranyl diphosphate synthase gene and the active enzyme expression level. J Biochem, 136 (3): 301-12. [PMID:15598886]
8. McKenna CE, Kashemirov BA, Błazewska KM, Mallard-Favier I, Stewart CA, Rojas J, Lundy MW, Ebetino FH, Baron RA, Dunford JE et al.. (2010) Synthesis, chiral high performance liquid chromatographic resolution and enantiospecific activity of a potent new geranylgeranyl transferase inhibitor, 2-hydroxy-3-imidazo[1,2-a]pyridin-3-yl-2-phosphonopropionic acid. J Med Chem, 53 (9): 3454-64. [PMID:20394422]
9. Szabo CM, Matsumura Y, Fukura S, Martin MB, Sanders JM, Sengupta S, Cieslak JA, Loftus TC, Lea CR, Lee HJ et al.. (2002) Inhibition of geranylgeranyl diphosphate synthase by bisphosphonates and diphosphates: a potential route to new bone antiresorption and antiparasitic agents. J Med Chem, 45 (11): 2185-96. [PMID:12014956]
10. Wiemer AJ, Tong H, Swanson KM, Hohl RJ. (2007) Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase. Biochem Biophys Res Commun, 353 (4): 921-5. [PMID:17208200]
11. Wiemer AJ, Yu JS, Lamb KM, Hohl RJ, Wiemer DF. (2008) Mono- and dialkyl isoprenoid bisphosphonates as geranylgeranyl diphosphate synthase inhibitors. Bioorg Med Chem, 16 (1): 390-9. [PMID:17905588]
12. Yoshida T, Asanuma M, Grossmann L, Fuse M, Shibata T, Yonekawa T, Tanaka T, Ueno K, Yasuda T, Saito Y et al.. (2006) Geranylgeranyl-pyrophosphate (GGPP) synthase is down-regulated during differentiation of osteoblastic cell line MC3T3-E1. FEBS Lett, 580 (22): 5203-7. [PMID:16978613]
13. Zhao Y, Yu L, Gao J, Fu Q, Hua Y, Zhang H, Zhao S. (2000) cDNA cloning, chromosome mapping and expression characterization of human geranylgeranyl pyrophosphate synthase. Sci China, C, Life Sci, 43 (6): 613-22. [PMID:18726356]