2OPM
Human Farnesyl Diphosphate Synthase Complexed with Bisphosphonate BPH-461
Summary for 2OPM
| Entry DOI | 10.2210/pdb2opm/pdb |
| Related | 2OPN |
| Descriptor | Farnesyl pyrophosphate synthetase (FPP synthetase) (FPS) (Farnesyl diphosphate synthetase) [Includes: Dimethylallyltranstransferase (EC 2.5.1.1); Geranyltranstransferase (EC 2.5.1.10)], PHOSPHATE ION, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | protein-bisphosphonate complex, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P14324 |
| Total number of polymer chains | 1 |
| Total formula weight | 43578.75 |
| Authors | Cao, R.,Gao, Y.G.,Robinson, H.,Goddard, A. (deposition date: 2007-01-29, release date: 2007-12-11, Last modification date: 2023-08-30) |
| Primary citation | Zhang, Y.,Cao, R.,Yin, F.,Hudock, M.P.,Guo, R.T.,Krysiak, K.,Mukherjee, S.,Gao, Y.G.,Robinson, H.,Song, Y.,No, J.H.,Bergan, K.,Leon, A.,Cass, L.,Goddard, A.,Chang, T.K.,Lin, F.Y.,Van Beek, E.,Papapoulos, S.,Wang, A.H.,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., 131:5153-5162, 2009 Cited by PubMed Abstract: 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. PubMed: 19309137DOI: 10.1021/ja808285e PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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