| Structural highlights
2zev is a 2 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Related: | 2dh4, 2e8t, 2e8u, 2e8v, 2e8w, 2e8x, 2e90, 2e91, 2e92, 2e93, 2e94, 2e95, 2zeu |
| Activity: | Heptaprenyl diphosphate synthase, with EC number 2.5.1.30 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[GGPPS_YEAST] Catalyzes the trans-addition of the 3 molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate. Required for the membrane attachment of YPT1 and SEC4. May be involved in vesicle trafficking and protein sorting.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and protein geranylgeranyl transferase (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Due to dual site targeting and decreased polarity, the compounds have activities far greater than do current bisphosphonate drugs in inhibiting tumor cell growth and invasiveness, both in vitro and in vivo. We explore how these compounds inhibit cell growth and how cell activity can be predicted based on enzyme inhibition data, and using X-ray diffraction, solid state NMR, and isothermal titration calorimetry, we show how these compounds bind to FPPS and/or GGPPS.
Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation.,Zhang Y, Cao R, Yin F, Hudock MP, Guo RT, Krysiak K, Mukherjee S, Gao YG, Robinson H, Song Y, No JH, Bergan K, Leon A, Cass L, Goddard A, Chang TK, Lin FY, Van Beek E, Papapoulos S, Wang AH, Kubo T, Ochi M, Mukkamala D, Oldfield E J Am Chem Soc. 2009 Apr 15;131(14):5153-62. PMID:19309137[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jiang Y, Proteau P, Poulter D, Ferro-Novick S. BTS1 encodes a geranylgeranyl diphosphate synthase in Saccharomyces cerevisiae. J Biol Chem. 1995 Sep 15;270(37):21793-9. PMID:7665600
- ↑ Shiflett SL, Vaughn MB, Huynh D, Kaplan J, Ward DM. Bph1p, the Saccharomyces cerevisiae homologue of CHS1/beige, functions in cell wall formation and protein sorting. Traffic. 2004 Sep;5(9):700-10. PMID:15296494 doi:http://dx.doi.org/10.1111/j.1600-0854.2004.00213.x
- ↑ Zhang Y, Cao R, Yin F, Hudock MP, Guo RT, Krysiak K, Mukherjee S, Gao YG, Robinson H, Song Y, No JH, Bergan K, Leon A, Cass L, Goddard A, Chang TK, Lin FY, Van Beek E, Papapoulos S, Wang AH, Kubo T, Ochi M, Mukkamala D, Oldfield E. Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation. J Am Chem Soc. 2009 Apr 15;131(14):5153-62. PMID:19309137 doi:10.1021/ja808285e
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