3icm: Difference between revisions
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==Trypanosoma cruzi farnesyl diphosphate synthase homodimer in complex with isopentenyl pyrophosphate, Mg2+ and 1-(2-Hydroxy-2,2-bis-phosphono-ethyl)-3-phenyl-pyridinium== | |||
<StructureSection load='3icm' size='340' side='right' caption='[[3icm]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3icm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ICM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ICM FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=P2H:1-(2-HYDROXY-2,2-DIPHOSPHONOETHYL)-3-PHENYLPYRIDINIUM'>P2H</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3iba|3iba]], [[3ick|3ick]], [[1yhl|1yhl]], [[1ykm|1ykm]], [[1yhk|1yhk]], [[3icn|3icn]], [[3icz|3icz]], [[3id0|3id0]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FPPS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5693 Trypanosoma cruzi])</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=3icm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3icm OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3icm RCSB], [http://www.ebi.ac.uk/pdbsum/3icm PDBsum]</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/ic/3icm_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/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Bisphosphonates (BPs) are a class of compounds that have been used extensively in the treatment of osteoporosis and malignancy-related hypercalcemia. Some of these compounds act through inhibition of farnesyl diphosphate synthase (FPPS), a key enzyme in the synthesis of isoprenoids. Recently, nitrogen-containing bisphosphonates (N-BPs) used in bone resorption therapy have been shown to be active against Trypanosoma cruzi, the parasite that causes American trypanosomiasis (Chagas disease), suggesting that they may be used as anti-trypanosomal agents. The crystal structures of TcFPPS in complex with substrate (isopentenyl diphosphate, IPP) and five N-BP inhibitors show that the C-1 hydroxyl and the nitrogen-containing groups of the inhibitors alter the binding of IPP and the conformation of two TcFPPS residues, Tyr94 and Gln167. Isothermal titration calorimetry experiments suggest that binding of the first N-BPs to the homodimeric TcFPPS changes the binding properties of the second site. This mechanism of binding of N-BPs to TcFPPS is different to that reported for the binding of the same compounds to human FPPS. Proteins 2010. (c) 2009 Wiley-Liss, Inc. | |||
Binding of nitrogen-containing bisphosphonates (N-BPs) to the Trypanosoma cruzi farnesyl diphosphate synthase homodimer.,Huang CH, Gabelli SB, Oldfield E, Amzel LM Proteins. 2010 Mar;78(4):888-99. PMID:19876942<ref>PMID:19876942</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Farnesyl diphosphate synthase|Farnesyl diphosphate synthase]] | *[[Farnesyl diphosphate synthase|Farnesyl diphosphate synthase]] | ||
== References == | |||
== | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Trypanosoma cruzi]] | [[Category: Trypanosoma cruzi]] | ||
[[Category: Amzel, L M | [[Category: Amzel, L M]] | ||
[[Category: Gabelli, S B | [[Category: Gabelli, S B]] | ||
[[Category: Huang, C H | [[Category: Huang, C H]] | ||
[[Category: Oldfield, E | [[Category: Oldfield, E]] | ||
[[Category: Bisphosphonate]] | [[Category: Bisphosphonate]] | ||
[[Category: Chagas disease]] | [[Category: Chagas disease]] | ||