2EWG
T. brucei Farnesyl Diphosphate Synthase Complexed with Minodronate
Summary for 2EWG
Entry DOI | 10.2210/pdb2ewg/pdb |
Descriptor | farnesyl pyrophosphate synthase, MAGNESIUM ION, (1-HYDROXY-2-IMIDAZO[1,2-A]PYRIDIN-3-YLETHANE-1,1-DIYL)BIS(PHOSPHONIC ACID), ... (5 entities in total) |
Functional Keywords | protein-bisphosphonate complex, transferase |
Biological source | Trypanosoma brucei |
Total number of polymer chains | 2 |
Total formula weight | 89969.88 |
Authors | Cao, R.,Mao, J.,Gao, Y.,Robinson, H.,Odeh, S.,Goddard, A.,Oldfield, E. (deposition date: 2005-11-03, release date: 2006-10-31, Last modification date: 2024-02-14) |
Primary citation | Mao, J.,Mukherjee, S.,Zhang, Y.,Cao, R.,Sanders, J.M.,Song, Y.,Zhang, Y.,Meints, G.A.,Gao, Y.G.,Mukkamala, D.,Hudock, M.P.,Oldfield, E. Solid-state NMR, crystallographic, and computational investigation of bisphosphonates and farnesyl diphosphate synthase-bisphosphonate complexes. J.Am.Chem.Soc., 128:14485-14497, 2006 Cited by PubMed Abstract: Bisphosphonates are a class of molecules in widespread use in treating bone resorption diseases and are also of interest as immunomodulators and anti-infectives. They function by inhibiting the enzyme farnesyl diphosphate synthase (FPPS), but the details of how these molecules bind are not fully understood. Here, we report the results of a solid-state (13)C, (15)N, and (31)P magic-angle sample spinning (MAS) NMR and quantum chemical investigation of several bisphosphonates, both as pure compounds and when bound to FPPS, to provide information about side-chain and phosphonate backbone protonation states when bound to the enzyme. We then used computational docking methods (with the charges assigned by NMR) to predict how several bisphosphonates bind to FPPS. Finally, we used X-ray crystallography to determine the structures of two potent bisphosphonate inhibitors, finding good agreement with the computational results, opening up the possibility of using the combination of NMR, quantum chemistry and molecular docking to facilitate the design of other, novel prenytransferase inhibitors. PubMed: 17090032DOI: 10.1021/ja061737c PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.48 Å) |
Structure validation
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