3n1v | pdb_00003n1v

Human FPPS COMPLEX WITH FBS_01

spinqualitylabelsall models 3n1v, resolution 2.18Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n1v is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 3N1, PO4 Related: 3n1w, 3n3l, 3n45, 3n46, 3n49, 3n5h, 3n5j, 3n6k Gene: FDPS, FPS, KIAA1293 (HUMAN) 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 Bisphosphonates are potent inhibitors of farnesyl pyrophosphate synthase (FPPS) and are highly efficacious in the treatment of bone diseases such as osteoporosis, Paget's disease and tumor-induced osteolysis. In addition, the potential for direct antitumor effects has been postulated on the basis of in vitro and in vivo studies and has recently been demonstrated clinically in early breast cancer patients treated with the potent bisphosphonate zoledronic acid. However, the high affinity of bisphosphonates for bone mineral seems suboptimal for the direct treatment of soft-tissue tumors. Here we report the discovery of the first potent non-bisphosphonate FPPS inhibitors. These new inhibitors bind to a previously unknown allosteric site on FPPS, which was identified by fragment-based approaches using NMR and X-ray crystallography. This allosteric and druggable pocket allows the development of a new generation of FPPS inhibitors that are optimized for direct antitumor effects in soft tissue. Allosteric non-bisphosphonate FPPS inhibitors identified by fragment-based discovery.,Jahnke W, Rondeau JM, Cotesta S, Marzinzik A, Pelle X, Geiser M, Strauss A, Gotte M, Bitsch F, Hemmig R, Henry C, Lehmann S, Glickman JF, Roddy TP, Stout SJ, Green JR Nat Chem Biol. 2010 Sep;6(9):660-6. Epub 2010 Aug 15. PMID:20711197 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Farnesyl diphosphate synthase

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