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| <StructureSection load='3dst' size='450' side='right' caption='Structure of rat geranylgeranyl transferase type 2 subunits α (magenta) and β (cyan) complex with geranylgeranyl pyrophosphate, Zn+2 (grey) and Ca+2 (green) ions (PDB code [[3dst]]).' scene='59/597443/Cv/1'> | | <StructureSection load='3dst' size='350' side='right' caption='Structure of rat geranylgeranyl transferase type 2 subunits α (magenta) and β (cyan) complex with geranylgeranyl pyrophosphate, Zn+2 (grey) and Ca+2 (green) ions (PDB code [[3dst]]).' scene='59/597443/Cv/1'> |
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| == Function == | | == Function == |
Revision as of 15:48, 12 January 2017
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Function
Geranylgeranyl transferase type 1 (GGT1) adds a 20-carbon isoprenoid group called geranylgeranyl (GG) to the C-terminal of proteins containg the CAAX motif (Cysteine, Aliphatic, Aliphatic, any amino acid). Geranylgeranyl transferase type 2 (GGT2) adds 2 GG groups to C-terminal cysteine residue of a protein. The addition of the hydrophobic prenyl group causes the proteins to become membrane-associated[1].
Relevance
GGT2 inhibitors block bone resorption and induces myeloma cell apoptosis[2].
Structural highlights
The active site with bound geranylgeranyl pyrophosphate contains a Zn+2 atom[3]. Water molecules shown as red spheres.
- ↑ Lane KT, Beese LS. Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res. 2006 Apr;47(4):681-99. Epub 2006 Feb 13. PMID:16477080 doi:https://dx.doi.org/10.1194/jlr.R600002-JLR200
- ↑ Lawson MA, Coulton L, Ebetino FH, Vanderkerken K, Croucher PI. Geranylgeranyl transferase type II inhibition prevents myeloma bone disease. Biochem Biophys Res Commun. 2008 Dec 12;377(2):453-7. doi:, 10.1016/j.bbrc.2008.09.157. Epub 2008 Oct 16. PMID:18929536 doi:https://dx.doi.org/10.1016/j.bbrc.2008.09.157
- ↑ Guo Z, Wu YW, Das D, Delon C, Cramer J, Yu S, Thuns S, Lupilova N, Waldmann H, Brunsveld L, Goody RS, Alexandrov K, Blankenfeldt W. Structures of RabGGTase-substrate/product complexes provide insights into the evolution of protein prenylation. EMBO J. 2008 Sep 17;27(18):2444-56. Epub 2008 Aug 28. PMID:18756270 doi:10.1038/emboj.2008.164
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3D structures of eranylgeranyl transferase
Updated on 12-January-2017
{"openlevels":0}
- Geranylgeranyl transferase type 1
- 1s64 – rGGT1 α+β subunits + inhibitor - rat
- 1n4p – rGGT1 α+β subunits + GGPP
- 1n4s, 1n4r – rGGT1 α+β subunits + GGPP + peptide-GG containing CAAX
- 1tnb, 1tno, 1tnu, 1tny, 1tnz, 1n4q – rGGT1 α+β subunits + GGPP analog + peptide containing CAAX
- 3dra – GGT1 α+β subunits + GGPP – Candida albicans
- Geranylgeranyl transferase type 2
- 1dce – rGGT2 α+β subunits – rat
- 3dss – rGGT2 α+β subunits
- Geranylgeranyl transferase type 2 complex
- 3c72, 3pz1, 3pz3, 4ehm, 4gts, 4gtt, 4gtv – rGGT2 α+β subunits + inhibitor
- 3hxb, 3hxc, 3hxd, 3hxe, 3hxf – rGGT2 α (mutant) +β subunits + inhibitor
- 1ltx – rGGT α+β subunits + tetra-alanine + Rab escort protein + farnesyl
- 3dst – rGGT2 α+β subunits + GGPP
- 3dsu – rGGT2 α+β subunits + farnesyl-PP
- 3dsv, 3dsw, 3dsx – rGGT2 α+β subunits + GG
- 3pz2 – rGGT2 α+β subunits + GGPP + inhibitor
References
proteopedia link