3icm | pdb_00003icm

Trypanosoma cruzi farnesyl diphosphate synthase homodimer in complex with isopentenyl pyrophosphate, Mg2+ and 1-(2-Hydroxy-2,2-bis-phosphono-ethyl)-3-phenyl-pyridinium

spinqualitylabelsall models 3icm, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3icm is a 1 chain structure with sequence from Trycr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: IPE, MG, P2H, SO4 Related: 3iba, 3ick, 1yhl, 1ykm, 1yhk, 3icn, 3icz, 3id0 Gene: FPPS (TRYCR) Activity: (2E,6E)-farnesyl diphosphate synthase, with EC number 2.5.1.10 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Binding of nitrogen-containing bisphosphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer.,Huang CH, Gabelli SB, Oldfield E, Amzel LM Proteins. 2010 Mar;78(4):888-99. PMID:19876942 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Farnesyl diphosphate synthase 3D structures

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