5afx: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==T. Brucei Farnesyl Diphosphate Synthase Complexed with Bisphosphonate BPH-1238== | ||
<StructureSection load='5afx' size='340' side='right' caption='[[5afx]], [[Resolution|resolution]] 2.39Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5afx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AFX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5AFX FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PVZ:[1-HYDROXY-2-(1-NONYL-1H-3LAMBDA~5~-IMIDAZOL-3-YL)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>PVZ</scene></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=5afx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5afx OCA], [http://pdbe.org/5afx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5afx RCSB], [http://www.ebi.ac.uk/pdbsum/5afx PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We report the results of a screen of a library of 925 potential prenyl synthase inhibitors against Trypanosoma brucei farnesyl diphosphate synthase (TbFPPS) and against T. brucei, the causative agent of human African trypanosomiasis. The most potent compounds were lipophilic analogs of the bone resorption drug zoledronate, some of which had submicromolar to low micromolar activity against bloodstream form T. brucei and selectivity indices of up to approximately 300. We evaluated the effects of two such inhibitors on survival and parasitemia in a T. brucei mouse model of infection and found that survival increased by up to 16 days. We also investigated the binding of three lipophilic bisphosphonates to an expressed TbFPPS using crystallography and investigated the thermodynamics of binding using isothermal titration calorimetry. | |||
In Vitro and In Vivo Investigation of the Inhibition of Trypanosoma brucei Cell Growth by Lipophilic Bisphosphonates.,Yang G, Zhu W, Kim K, Byun SY, Choi G, Wang K, Cha JS, Cho HS, Oldfield E, No JH Antimicrob Agents Chemother. 2015 Dec;59(12):7530-9. doi: 10.1128/AAC.01873-15., Epub 2015 Sep 21. PMID:26392508<ref>PMID:26392508</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5afx" style="background-color:#fffaf0;"></div> | |||
[[Category: | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: No, J H]] | |||
[[Category: Oldfield, E]] | |||
[[Category: Yang, G]] | [[Category: Yang, G]] | ||
[[Category: | [[Category: Transferase]] | ||
Revision as of 12:55, 2 December 2015
T. Brucei Farnesyl Diphosphate Synthase Complexed with Bisphosphonate BPH-1238T. Brucei Farnesyl Diphosphate Synthase Complexed with Bisphosphonate BPH-1238
Structural highlights
Publication Abstract from PubMedWe report the results of a screen of a library of 925 potential prenyl synthase inhibitors against Trypanosoma brucei farnesyl diphosphate synthase (TbFPPS) and against T. brucei, the causative agent of human African trypanosomiasis. The most potent compounds were lipophilic analogs of the bone resorption drug zoledronate, some of which had submicromolar to low micromolar activity against bloodstream form T. brucei and selectivity indices of up to approximately 300. We evaluated the effects of two such inhibitors on survival and parasitemia in a T. brucei mouse model of infection and found that survival increased by up to 16 days. We also investigated the binding of three lipophilic bisphosphonates to an expressed TbFPPS using crystallography and investigated the thermodynamics of binding using isothermal titration calorimetry. In Vitro and In Vivo Investigation of the Inhibition of Trypanosoma brucei Cell Growth by Lipophilic Bisphosphonates.,Yang G, Zhu W, Kim K, Byun SY, Choi G, Wang K, Cha JS, Cho HS, Oldfield E, No JH Antimicrob Agents Chemother. 2015 Dec;59(12):7530-9. doi: 10.1128/AAC.01873-15., Epub 2015 Sep 21. PMID:26392508[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||