5cg5
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Neutron crystal structure of human farnesyl pyrophosphate synthase in complex with risedronate== |
| + | <StructureSection load='5cg5' size='340' side='right' caption='[[5cg5]], [[Resolution|resolution]] 1.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5cg5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CG5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CG5 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DOD:DEUTERATED+WATER'>DOD</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RIS:1-HYDROXY-2-(3-PYRIDINYL)ETHYLIDENE+BIS-PHOSPHONIC+ACID'>RIS</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cg6|5cg6]]</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5cg5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cg5 OCA], [http://pdbe.org/5cg5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cg5 RCSB], [http://www.ebi.ac.uk/pdbsum/5cg5 PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/FPPS_HUMAN 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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:26314394</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5cg5" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| - | [[Category: Schrader, T | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Kusaka, K]] | ||
| + | [[Category: Mizuguchi, M]] | ||
| + | [[Category: Niimura, N]] | ||
| + | [[Category: Ostermann, A]] | ||
| + | [[Category: Schrader, T E]] | ||
[[Category: Tanaka, I]] | [[Category: Tanaka, I]] | ||
[[Category: Yokoyama, T]] | [[Category: Yokoyama, T]] | ||
| - | [[Category: | + | [[Category: Bisphophonate]] |
| - | [[Category: | + | [[Category: Inhibitor]] |
| - | [[Category: | + | [[Category: Osteoprosis]] |
| - | [[Category: | + | [[Category: Prenyl transferase]] |
| + | [[Category: Transferase-transferase inhibotor complex]] | ||
Revision as of 03:54, 16 October 2015
Neutron crystal structure of human farnesyl pyrophosphate synthase in complex with risedronate
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