4RXA
Crystal structure of human farnesyl diphosphate synthase in complex with BPH-1358
Summary for 4RXA
| Entry DOI | 10.2210/pdb4rxa/pdb |
| Descriptor | Farnesyl pyrophosphate synthase, N,N'-bis[3-(4,5-dihydro-1H-imidazol-2-yl)phenyl]biphenyl-4,4'-dicarboxamide, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | prenylation, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P14324 |
| Total number of polymer chains | 1 |
| Total formula weight | 40653.27 |
| Authors | Liu, Y.-L.,Cao, R.,Wang, Y.,Oldfield, E. (deposition date: 2014-12-09, release date: 2015-04-15, Last modification date: 2024-02-28) |
| Primary citation | Liu, Y.L.,Cao, R.,Wang, Y.,Oldfield, E. Farnesyl diphosphate synthase inhibitors with unique ligand-binding geometries. ACS Med Chem Lett, 6:349-354, 2015 Cited by PubMed Abstract: Farnesyl diphosphate synthase (FPPS) is an important drug target for bone resorption, cancer, and some infectious diseases. Here, we report five new structures including two having unique bound ligand geometries. The diamidine inhibitor 7 binds to human FPPS close to the homoallylic (S2) and allosteric (S3) sites and extends into a new site, here called S4. With the bisphosphonate inhibitor 8, two molecules bind to Trypanosoma brucei FPPS, one molecule in the allylic site (S1) and the other close to S2, the first observation of two bisphosphonate molecules bound to FPPS. We also report the structures of apo-FPPS from T. brucei, together with two more bisphosphonate-bound structures (2,9), for purposes of comparison. The diamidine structure is of particular interest because 7 could represent a new lead for lipophilic FPPS inhibitors, while 8 has low micromolar activity against T. brucei, the causative agent of human African trypanosomiasis. PubMed: 25815158DOI: 10.1021/ml500528x PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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