View source for 2ewg


==T. brucei Farnesyl Diphosphate Synthase Complexed with Minodronate==
<StructureSection load='2ewg' size='340' side='right'caption='[[2ewg]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2ewg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EWG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2EWG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=M0N:(1-HYDROXY-2-IMIDAZO[1,2-A]PYRIDIN-3-YLETHANE-1,1-DIYL)BIS(PHOSPHONIC+ACID)'>M0N</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PGO:S-1,2-PROPANEDIOL'>PGO</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='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=2ewg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ewg OCA], [http://pdbe.org/2ewg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ewg RCSB], [http://www.ebi.ac.uk/pdbsum/2ewg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ewg ProSAT]</span></td></tr>
</table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ew/2ewg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ewg ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Bisphosphonates 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<ref>PMID:17090032</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2ewg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Cao, R]]
[[Category: Gao, Y]]
[[Category: Goddard, A]]
[[Category: Mao, J]]
[[Category: Odeh, S]]
[[Category: Oldfield, E]]
[[Category: Robinson, H]]
[[Category: Protein-bisphosphonate complex]]
[[Category: Transferase]]