4H5C
Crystal structure of human FPPS in ternary complex with YS0470 and inorganic phosphate
Summary for 4H5C
| Entry DOI | 10.2210/pdb4h5c/pdb |
| Related | 4DEM 4H5D 4H5E |
| Descriptor | Farnesyl pyrophosphate synthase, [({4-[4-(propan-2-yloxy)phenyl]pyridin-2-yl}amino)methanediyl]bis(phosphonic acid), PHOSPHATE ION, ... (5 entities in total) |
| Functional Keywords | transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P14324 |
| Total number of polymer chains | 1 |
| Total formula weight | 43715.14 |
| Authors | Park, J.,Lin, Y.-S.,Tsantrizos, Y.S.,Berghuis, A.M. (deposition date: 2012-09-18, release date: 2012-12-26, Last modification date: 2023-09-20) |
| Primary citation | Park, J.,Lin, Y.S.,De Schutter, J.W.,Tsantrizos, Y.S.,Berghuis, A.M. Ternary complex structures of human farnesyl pyrophosphate synthase bound with a novel inhibitor and secondary ligands provide insights into the molecular details of the enzyme's active site closure. Bmc Struct.Biol., 12:32-32, 2012 Cited by PubMed Abstract: Human farnesyl pyrophosphate synthase (FPPS) controls intracellular levels of farnesyl pyrophosphate, which is essential for various biological processes. Bisphosphonate inhibitors of human FPPS are valuable therapeutics for the treatment of bone-resorption disorders and have also demonstrated efficacy in multiple tumor types. Inhibition of human FPPS by bisphosphonates in vivo is thought to involve closing of the enzyme's C-terminal tail induced by the binding of the second substrate isopentenyl pyrophosphate (IPP). This conformational change, which occurs through a yet unclear mechanism, seals off the enzyme's active site from the solvent environment and is essential for catalysis. The crystal structure of human FPPS in complex with a novel bisphosphonate YS0470 and in the absence of a second substrate showed partial ordering of the tail in the closed conformation. PubMed: 23234314DOI: 10.1186/1472-6807-12-32 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.02 Å) |
Structure validation
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