1RTR
Crystal Structure of S. Aureus Farnesyl Pyrophosphate Synthase
Summary for 1RTR
| Entry DOI | 10.2210/pdb1rtr/pdb |
| Related | 1RQI 1RQJ |
| Descriptor | geranyltranstransferase (2 entities in total) |
| Functional Keywords | transferase |
| Biological source | Staphylococcus aureus |
| Total number of polymer chains | 2 |
| Total formula weight | 67722.70 |
| Authors | Hosfield, D.J.,Zhang, Y.,Dougan, D.R.,Brooun, A.,Tari, L.W.,Swanson, R.V.,Finn, J. (deposition date: 2003-12-10, release date: 2004-03-02, Last modification date: 2024-02-14) |
| Primary citation | Hosfield, D.J.,Zhang, Y.,Dougan, D.R.,Brooun, A.,Tari, L.W.,Swanson, R.V.,Finn, J. Structural basis for bisphosphonate-mediated inhibition of isoprenoid biosynthesis J.Mol.Biol., 279:8526-8529, 2004 Cited by PubMed Abstract: Farnesyl pyrophosphate synthetase (FPPS) synthesizes farnesyl pyrophosphate through successive condensations of isopentyl pyrophosphate with dimethylallyl pyrophosphate and geranyl pyrophosphate. Nitrogen-containing bisphosphonate drugs used to treat osteoclast-mediated bone resorption and tumor-induced hypercalcemia are potent inhibitors of the enzyme. Here we present crystal structures of substrate and bisphosphonate complexes of FPPS. The structures reveal how enzyme conformational changes organize conserved active site residues to exploit metal-induced ionization and substrate positioning for catalysis. The structures further demonstrate how nitrogen-containing bisphosphonates mimic a carbocation intermediate to inhibit the enzyme. Together, these FPPS complexes provide a structural template for the design of novel inhibitors that may prove useful for the treatment of osteoporosis and other clinical indications including cancer. PubMed: 14672944DOI: 10.1074/jbc.C300511200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
Download full validation report
