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=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2i19]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2i19]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei Trypanosoma brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2I19 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2I19 FirstGlance]. <br> | ||
</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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.28Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2i19 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2i19 OCA], [https://pdbe.org/2i19 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2i19 RCSB], [https://www.ebi.ac.uk/pdbsum/2i19 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2i19 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/Q86C09_9TRYP Q86C09_9TRYP] | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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> | ||
</jmolCheckbox> | </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/ | </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=2i19 ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
| Line 25: | Line 28: | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2i19" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Farnesyl diphosphate synthase|Farnesyl diphosphate synthase]] | *[[Farnesyl diphosphate synthase 3D structures|Farnesyl diphosphate synthase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Trypanosoma brucei]] | [[Category: Trypanosoma brucei]] | ||
[[Category: Cao | [[Category: Cao R]] | ||
[[Category: Gao | [[Category: Gao Y]] | ||
[[Category: Goddard | [[Category: Goddard A]] | ||
[[Category: Mao | [[Category: Mao J]] | ||
[[Category: Odeh | [[Category: Odeh S]] | ||
[[Category: Oldfield | [[Category: Oldfield E]] | ||
[[Category: Robinson | [[Category: Robinson H]] | ||
Latest revision as of 13:04, 30 August 2023
T. Brucei farnesyl diphosphate synthase complexed with bisphosphonateT. Brucei farnesyl diphosphate synthase complexed with bisphosphonate
Structural highlights
FunctionEvolutionary 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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