5cg6 | pdb_00005cg6

Neutron crystal structure of human farnesyl pyrophosphate synthase in complex with risedronate and isopentenyl pyrophosphate

spinqualitylabelsall models 5cg6, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cg6 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. Ligands: DOD, IPE, MG, RIS 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. Publication Abstract from PubMed Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate to FPP and is known to be a molecular target of osteoporosis drugs, such as risedronate (RIS), which is a nitrogen-containing bisphosphonate. The protonation states and hydration structure of RIS bound to FPPS were determined by neutron protein crystallography, which allows direct visualization of hydrogens and deuteriums. The structure analysis revealed that the phosphate groups of RIS were fully deprotonated with the abnormally decreased pKa, and that the roles of E93 and D264 consisted of canceling the extra negative charges upon the binding of ligands. Collectively, our neutron structures provided insights into the physicochemical properties during the bisphosphonate binding event. Protonation State and Hydration of Bisphosphonate Bound to Farnesyl Pyrophosphate Synthase.,Yokoyama T, Mizuguchi M, Ostermann A, Kusaka K, Niimura N, Schrader TE, Tanaka I J Med Chem. 2015 Sep 24;58(18):7549-56. doi: 10.1021/acs.jmedchem.5b01147. Epub, 2015 Sep 4. PMID:26314394 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Farnesyl diphosphate synthase 3D structures

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