ゲラニルゲラニルトランスフェラーゼ、ゲラニルゲラニル転移酵素
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/04/10 14:43:02」(JST)
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| protein geranylgeranyltransferase type I |
| Identifiers |
| EC number |
2.5.1.59 |
| CAS number |
135371-29-8 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
|
| GGTase 1 α-subunit (farnesyltransferase, CAAX box) |
| Identifiers |
| Symbol |
FNTA |
| Entrez |
2339 |
| HUGO |
3782 |
| OMIM |
134635 |
| PDB |
1S64 (RCSB PDB PDBe PDBj) |
| RefSeq |
NM_002027 |
| UniProt |
P49354 |
| Other data |
| EC number |
2.5.1.59 |
| Locus |
Chr. 8 p11.21 |
GGTase 1 β-subunit
(protein geranylgeranyl- transferase type I, β subunit) |
| Identifiers |
| Symbol |
PGGT1B |
| Entrez |
5229 |
| HUGO |
8895 |
| OMIM |
602031 |
| PDB |
1S64 (RCSB PDB PDBe PDBj) |
| RefSeq |
NM_005023 |
| UniProt |
P53609 |
| Other data |
| EC number |
2.5.1.59 |
| Locus |
Chr. 5 q23.1 |
Geranylgeranyltransferase may be used to refer to either Geranylgeranyltransferase type 1 or Rab geranylgeranyltransferase
Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase is one of the three enzymes in the prenyltransferase group. In specific terms, Geranylgeranyltransferase (GGTase 1) adds a 20-carbon isoprenoid called a geranylgeranyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminal of a protein. Geranylgeranyltransferase inhibitors are being investigated as anti-cancer agents.[1]
Contents
- 1 Function
- 2 Structure
- 3 References
- 4 Further reading
- 5 See also
Function
Prenyltransferases, including geranylgeranyltransferase, posttranslationally modify proteins by adding an isoprenoid lipid called a prenyl group to the carboxyl terminus of the target protein. This process, called prenylation, causes prenylated proteins to become membrane-associated due to the hydophobic nature of the prenyl group. Most prenylated proteins are involved in cellular signaling, wherein membrane association is critical for function.[1]
Structure
Geranylgeranyltransferase contains two subunits, α and β that are encoded by the FNTA and PGGT1B genes, respectively. Both subunits are composed primarily of alpha helices. Geranylgeranyltransferase coordinates a zinc cation on its β subunit at the lip of the active site. Geranylgeranyltransferase has a hydrophobic binding pocket for geranylgeranyl diphosphate, the lipid donor molecule. All Geranylgeranyltransferase substrates invariably have a cysteine as their fourth-to-last residue. This cysteine, coordinated by the zinc, engages in an SN2 type attack on the geranylgeranyl diphosphate, displacing the diphosphate.[2][3]
References
- ^ a b Lane KT, Beese LS (April 2006). "Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I". J. Lipid Res. 47 (4): 681–99. doi:10.1194/jlr.R600002-JLR200. PMID 16477080.
- ^ Reid TS, Terry KL, Casey PJ, Beese LS (October 2004). "Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity". J. Mol. Biol. 343 (2): 417–33. doi:10.1016/j.jmb.2004.08.056. PMID 15451670.
- ^ Long SB, Casey PJ, Beese LS (October 2002). "Reaction path of protein farnesyltransferase at atomic resolution". Nature 419 (6907): 645–50. doi:10.1038/nature00986. PMID 12374986.
Further reading
- Eastman RT, Buckner FS, Yokoyama K, Gelb MH, Van Voorhis WC (February 2006). "Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation". J. Lipid Res. 47 (2): 233–40. doi:10.1194/jlr.R500016-JLR200. PMID 16339110.
- El Oualid F, Cohen LH, van der Marel GA, Overhand M (2006). "Inhibitors of protein: geranylgeranyl transferases". Curr. Med. Chem. 13 (20): 2385–427. doi:10.2174/092986706777935078. PMID 16918362.
See also
- Prenylation
- Farnesyltransferase
- Rab geranylgeranyltransferase - Geranylgeranyltransferase type 2
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Transferases: alkyl and aryl (EC 2.5)
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| 2.5.1 |
- Dimethylallyltranstransferase
- Thiaminase I
- Methionine adenosyltransferase
- Riboflavin synthase
- Dihydropteroate synthase
- Spermidine synthase
- Glutathione S-transferase
- Farnesyl-diphosphate farnesyltransferase
- Spermine synthase
- Alkylglycerone phosphate synthase
- Farnesyltransferase
- Geranylgeranyltransferase type 1
- Porphobilinogen deaminase
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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English Journal
- Astrocyte GGTI-mediated Rac1 prenylation upregulates NF-κB expression and promotes neuronal apoptosis following hypoxia/ischemia.
- Gao S1, Mo J2, Chen L2, Wang Y3, Mao X2, Shi Y2, Zhang X2, Yu R4, Zhou X5.
- Neuropharmacology.Neuropharmacology.2016 Apr;103:44-56. doi: 10.1016/j.neuropharm.2015.12.002. Epub 2015 Dec 12.
- Stroke is the fifth leading cause of death for Americans, and about 87% of all strokes are ischemic strokes. Astrogliosis plays a crucial role in the pathophysiology of delayed neuronal death (DND) following ischemic stroke. Here we reported that astrocyte geranylgeranyltransferase I (GGTI)-mediated
- PMID 26690896
- Advantages and Challenges of Phenotypic Screens: The Identification of Two Novel Antifungal Geranylgeranyltransferase I Inhibitors.
- Pries V1, Cotesta S1, Riedl R1, Aust T1, Schuierer S1, Tao J2, Filipuzzi I1, Hoepfner D3.
- Journal of biomolecular screening.J Biomol Screen.2016 Mar;21(3):306-15. doi: 10.1177/1087057115610488. Epub 2015 Oct 12.
- Phenotypic screens are effective starting points to identify compounds with desirable activities. To find novel antifungals, we conducted a phenotypic screen in Saccharomyces cerevisiae and identified two discrete scaffolds with good growth inhibitory characteristics. Lack of broad-spectrum activity
- PMID 26459507
- Statins inhibit blastocyst formation by preventing geranylgeranylation.
- Alarcon VB1, Marikawa Y2.
- Molecular human reproduction.Mol Hum Reprod.2016 Feb 7. pii: gaw011. [Epub ahead of print]
- STUDY HYPOTHESIS: Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase of the mevalonate pathway and prescription drugs that treat hypercholesterolemia, compromise preimplantation mouse development via modulation of HIPPO signaling.STUDY FINDING: HMG-CoA reductase activit
- PMID 26908642
Japanese Journal
- Geranylgeranyltransferase Cwg2-Rho4/Rho5 module is implicated in the Pmk1 MAP kinase-mediated cell wall integrity pathway in fission yeast
- Doi Akira,Kita Ayako,Kanda Yuki,Uno Takaya,Asami Keita,Satoh Ryosuke,Nakano Kentaro,Sugiura Reiko
- Genes to cells 20(4), 310-323, 2015-04
- … Here, we identified the vic2-1 mutants carrying a mis-sense mutation in the cwg2+ gene encoding a beta subunit of geranylgeranyltransferase I (GGTase I), which participates in the post-translational C-terminal modification of several small GTPases, allowing their targeting to the membrane. …
- NAID 120005608185
- Alteration of Enzyme Expressions in Mevalonate Pathway : Possible Role for Cardiovascular Remodeling in Spontaneously Hypertensive Rats
- , , ,
- Circulation journal : official journal of the Japanese Circulation Society 75(6), 1409-1417, 2011-05-25
- … In the heart, there was overexpression of some enzymes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), farnesyl diphosphate synthase (FDPS), and geranylgeranyltransferase type I (GGTase-I), and downregulation of squalene synthetase (SQS) in SHR since 3 weeks of age. …
- NAID 10028148921
- Molecular characterization and mRNA expression analysis of farnesyl transferase and geranylgeranyl transferase genes in the silkworm Bombyx mori
- , , ,
- Journal of Insect Biotechnology and Sericology 79(3), 3_095-3_102, 2011
- … Protein prenyl transferase, that is, farnesyltransferase (FT) and geranylgeranyltransferase (GGT), catalyze the farnesylation or geranylgeranylation of proteins including GTP-binding proteins (G proteins). …
- NAID 130004464169
Related Links
- Geranylgeranyltransferase type 1 or simply geranylgeranyltransferase, or 'matt's a bender', is one of the three enzymes in the prenyltransferase group. In specific terms, Geranylgeranyltransferase (GGTase 1) adds a 20-carbon ...
- Geranylgeranyltransferase type I (GGTase-I) deficiency hyperactivates macrophages and induces erosive arthritis in mice Omar M. Khan, 1 Mohamed X. Ibrahim, 1 Ing-Marie Jonsson, 2 Christin Karlsson, 1 Meng Liu, 1,3 1 1 2 2 ...
★リンクテーブル★
[★]
- 英
- geranylgeranyltransferase
- 関
- ゲラニルゲラニルトランスフェラーゼ
[★]
- 英
- geranylgeranyltransferase
- 関
- ゲラニルゲラニル転移酵素
[★]
ゲラニルゲラニル二リン酸ゲラニルゲラニルトランスフェラーゼ
- 関
- geranylgeranyl pyrophosphate synthase