2i19: Difference between revisions
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==T. Brucei farnesyl diphosphate synthase complexed with bisphosphonate== | ==T. Brucei farnesyl diphosphate synthase complexed with bisphosphonate== | ||
<StructureSection load='2i19' size='340' side='right' caption='[[2i19]], [[Resolution|resolution]] 2.28Å' scene=''> | <StructureSection load='2i19' size='340' side='right' caption='[[2i19]], [[Resolution|resolution]] 2.28Å' scene=''> | ||
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BY:[2-(PYRIDIN-2-YLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>1BY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1BY:[2-(PYRIDIN-2-YLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>1BY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(2E,6E)-farnesyl_diphosphate_synthase (2E,6E)-farnesyl diphosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.10 2.5.1.10] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(2E,6E)-farnesyl_diphosphate_synthase (2E,6E)-farnesyl diphosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.10 2.5.1.10] </span></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=2i19 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i19 OCA], [http://pdbe.org/2i19 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i19 RCSB], [http://www.ebi.ac.uk/pdbsum/2i19 PDBsum]</span></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=2i19 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i19 OCA], [http://pdbe.org/2i19 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2i19 RCSB], [http://www.ebi.ac.uk/pdbsum/2i19 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2i19 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i1/2i19_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/i1/2i19_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
Revision as of 11:15, 4 July 2018
T. Brucei farnesyl diphosphate synthase complexed with bisphosphonateT. Brucei farnesyl diphosphate synthase complexed with bisphosphonate
Structural highlights
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 PubMedBisphosphonates are a class of molecules in widespread use in treating bone resorption diseases and are also of interest as immunomodulators and anti-infectives. They function by inhibiting the enzyme farnesyl diphosphate synthase (FPPS), but the details of how these molecules bind are not fully understood. Here, we report the results of a solid-state (13)C, (15)N, and (31)P magic-angle sample spinning (MAS) NMR and quantum chemical investigation of several bisphosphonates, both as pure compounds and when bound to FPPS, to provide information about side-chain and phosphonate backbone protonation states when bound to the enzyme. We then used computational docking methods (with the charges assigned by NMR) to predict how several bisphosphonates bind to FPPS. Finally, we used X-ray crystallography to determine the structures of two potent bisphosphonate inhibitors, finding good agreement with the computational results, opening up the possibility of using the combination of NMR, quantum chemistry and molecular docking to facilitate the design of other, novel prenytransferase inhibitors. Solid-state NMR, crystallographic, and computational investigation of bisphosphonates and farnesyl diphosphate synthase-bisphosphonate complexes.,Mao J, Mukherjee S, Zhang Y, Cao R, Sanders JM, Song Y, Zhang Y, Meints GA, Gao YG, Mukkamala D, Hudock MP, Oldfield E J Am Chem Soc. 2006 Nov 15;128(45):14485-97. PMID:17090032[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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