2opm

Human Farnesyl Diphosphate Synthase Complexed with Bisphosphonate BPH-461

spinqualitylabelsall models 2opm, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2opm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: MG, NI9, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FPPS_HUMAN Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones. FPP also serves as substrate for protein farnesylation and geranylgeranylation. Catalyzes the sequential condensation of isopentenyl pyrophosphate with the allylic pyrophosphates, dimethylallyl pyrophosphate, and then with the resultant geranylpyrophosphate to the ultimate product farnesyl pyrophosphate. 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 Considerable effort has focused on the development of selective protein farnesyl transferase (FTase) and protein geranylgeranyl transferase (GGTase) inhibitors as cancer chemotherapeutics. Here, we report a new strategy for anticancer therapeutic agents involving inhibition of farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS), the two enzymes upstream of FTase and GGTase, by lipophilic bisphosphonates. Due to dual site targeting and decreased polarity, the compounds have activities far greater than do current bisphosphonate drugs in inhibiting tumor cell growth and invasiveness, both in vitro and in vivo. We explore how these compounds inhibit cell growth and how cell activity can be predicted based on enzyme inhibition data, and using X-ray diffraction, solid state NMR, and isothermal titration calorimetry, we show how these compounds bind to FPPS and/or GGPPS. Lipophilic bisphosphonates as dual farnesyl/geranylgeranyl diphosphate synthase inhibitors: an X-ray and NMR investigation.,Zhang Y, Cao R, Yin F, Hudock MP, Guo RT, Krysiak K, Mukherjee S, Gao YG, Robinson H, Song Y, No JH, Bergan K, Leon A, Cass L, Goddard A, Chang TK, Lin FY, Van Beek E, Papapoulos S, Wang AH, Kubo T, Ochi M, Mukkamala D, Oldfield E J Am Chem Soc. 2009 Apr 15;131(14):5153-62. PMID:19309137 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Farnesyl diphosphate synthase Farnesyl diphosphate synthase 3D structures

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