3ICN
Trypanosoma cruzi farnesyl diphosphate synthase homodimer in complex with isopentenyl pyrophosphate and 3-Fluoro-1-(2-hydroxy-2,2-bis-phosphono-ethyl)-pyridinium
Summary for 3ICN
| Entry DOI | 10.2210/pdb3icn/pdb |
| Related | 1YHK 1YHL 1YHM 3IBA 3ICK 3ICM 3ICZ 3ID0 |
| Descriptor | Farnesyl pyrophosphate synthase, 3-FLUORO-1-(2-HYDROXY-2,2-DIPHOSPHONOETHYL)PYRIDINIUM, MAGNESIUM ION, ... (6 entities in total) |
| Functional Keywords | farnesyl diphosphate synthase, fpps, bisphosphonate, zoledronate, risedronate, minodronate, chagas disease, isoprene biosynthesis, transferase |
| Biological source | Trypanosoma cruzi |
| Total number of polymer chains | 1 |
| Total formula weight | 42038.57 |
| Authors | Amzel, L.M.,Huang, C.H.,Gabelli, S.B.,Oldfield, E. (deposition date: 2009-07-17, release date: 2010-02-09, Last modification date: 2024-02-21) |
| Primary citation | Huang, C.H.,Gabelli, S.B.,Oldfield, E.,Amzel, L.M. Binding of nitrogen-containing bisphosphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer. Proteins, 78:888-899, 2010 Cited by PubMed Abstract: Bisphosphonates (BPs) are a class of compounds that have been used extensively in the treatment of osteoporosis and malignancy-related hypercalcemia. Some of these compounds act through inhibition of farnesyl diphosphate synthase (FPPS), a key enzyme in the synthesis of isoprenoids. Recently, nitrogen-containing bisphosphonates (N-BPs) used in bone resorption therapy have been shown to be active against Trypanosoma cruzi, the parasite that causes American trypanosomiasis (Chagas disease), suggesting that they may be used as anti-trypanosomal agents. The crystal structures of TcFPPS in complex with substrate (isopentenyl diphosphate, IPP) and five N-BP inhibitors show that the C-1 hydroxyl and the nitrogen-containing groups of the inhibitors alter the binding of IPP and the conformation of two TcFPPS residues, Tyr94 and Gln167. Isothermal titration calorimetry experiments suggest that binding of the first N-BPs to the homodimeric TcFPPS changes the binding properties of the second site. This mechanism of binding of N-BPs to TcFPPS is different to that reported for the binding of the same compounds to human FPPS. Proteins 2010. (c) 2009 Wiley-Liss, Inc. PubMed: 19876942DOI: 10.1002/prot.22614 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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