4e1e - Revision history

OCA at 14:49, 14 March 2024

2024-03-14T14:49:45Z

← Older revision		Revision as of 14:49, 14 March 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e1e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E1E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e1e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E1E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MW:[2-(HEXYLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>0MW</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.65Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MW:[2-(HEXYLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>0MW</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1e OCA], [https://pdbe.org/4e1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e1e RCSB], [https://www.ebi.ac.uk/pdbsum/4e1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1e ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1e OCA], [https://pdbe.org/4e1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e1e RCSB], [https://www.ebi.ac.uk/pdbsum/4e1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1e ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/Q95WL3_TRYCR Q95WL3_TRYCR]]		[https://www.uniprot.org/uniprot/Q95WL3_TRYCR Q95WL3_TRYCR]
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Linear 2-alkylaminoethyl-1,1-bisphosphonates are effective agents against proliferation of Trypanosoma cruzi , the etiologic agent of American trypanosomiasis (Chagas disease), exhibiting IC(50) values in the nanomolar range against the parasites. This activity is associated with inhibition at the low nanomolar level of the T. cruzi farnesyl diphosphate synthase (TcFPPS). X-ray structures and thermodynamic data of the complexes TcFPPS with five compounds of this family show that the inhibitors bind to the allylic site of the enzyme, with their alkyl chain occupying the cavity that binds the isoprenoid chain of the substrate. The compounds bind to TcFPPS with unfavorable enthalpy compensated by a favorable entropy that results from a delicate balance between two opposing effects: the loss of conformational entropy due to freezing of single bond rotations and the favorable burial of the hydrophobic alkyl chains. The data suggest that introduction of strategically placed double bonds and methyl branches should increase affinity substantially.

	Design, synthesis, calorimetry, and crystallographic analysis of 2-alkylaminoethyl-1,1-bisphosphonates as inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase.,Aripirala S, Szajnman SH, Jakoncic J, Rodriguez JB, Docampo R, Gabelli SB, Amzel LM J Med Chem. 2012 Jul 26;55(14):6445-54. Epub 2012 Jul 5. PMID:22715997<ref>PMID:22715997</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e1e" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
	*[[Farnesyl diphosphate synthase 3D structures\|Farnesyl diphosphate synthase 3D structures]]		*[[Farnesyl diphosphate synthase 3D structures\|Farnesyl diphosphate synthase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:44, 28 September 2022

2022-09-28T06:44:50Z

← Older revision		Revision as of 06:44, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+==		==Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+==
	<StructureSection load='4e1e' size='340' side='right' caption='[[4e1e]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='4e1e' size='340' side='right'caption='[[4e1e]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e1e]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Trycr Trycr~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1E OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E1E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e1e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_cruzi Trypanosoma cruzi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E1E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MW:[2-(HEXYLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>0MW</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene~~></td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0MW:[2-(HEXYLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>0MW</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1yhk\|1yhk]], [[1yhl\|1yhl]], [[1yhm\|1yhm]], [[3iba\|3iba]], [[3ick\|3ick]], [[3icm\|3icm]], [[3icn\|3icn]], [[3icz\|3icz]], [[4dwb\|4dwb]], [[4dwg\|4dwg]], [[4dxj\|4dxj]], [[4dzw\|4dzw]]</td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1e OCA], [https://pdbe.org/4e1e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e1e RCSB], [https://www.ebi.ac.uk/pdbsum/4e1e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1e ProSAT]</span></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 TRYCR])</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=4e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1e OCA], [~~http~~://pdbe.org/4e1e PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e1e RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e1e PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1e ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/Q95WL3_TRYCR Q95WL3_TRYCR]]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 21:		Line 20:

	==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: ~~Trycr~~]]		[[Category: Large Structures]]
	[[Category: ~~Amzel, L M~~]]		[[Category: Trypanosoma cruzi]]
	[[Category: ~~Aripirala, S~~]]		[[Category: Amzel LM]]
	[[Category: ~~Gabelli,~~ S B]]		[[Category: Aripirala S]]
	[[Category: ~~Farnesyl pyrophosphate synthase]]~~		[[Category: Gabelli SB]]
	~~[[Category: Geranyl transferase]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 15:52, 11 August 2016

2016-08-11T15:52:05Z

← Older revision		Revision as of 15:52, 11 August 2016
Line 1:		Line 1:

	==Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+==		==Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+==
	<StructureSection load='4e1e' size='340' side='right' caption='[[4e1e]], [[Resolution\|resolution]] 2.65Å' scene=''>		<StructureSection load='4e1e' size='340' side='right' caption='[[4e1e]], [[Resolution\|resolution]] 2.65Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e1e]] 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=4E1E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E1E FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e1e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Trycr Trycr]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E1E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E1E FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MW:[2-(HEXYLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>0MW</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MW:[2-(HEXYLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>0MW</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1yhk\|1yhk]], [[1yhl\|1yhl]], [[1yhm\|1yhm]], [[3iba\|3iba]], [[3ick\|3ick]], [[3icm\|3icm]], [[3icn\|3icn]], [[3icz\|3icz]], [[4dwb\|4dwb]], [[4dwg\|4dwg]], [[4dxj\|4dxj]], [[4dzw\|4dzw]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1yhk\|1yhk]], [[1yhl\|1yhl]], [[1yhm\|1yhm]], [[3iba\|3iba]], [[3ick\|3ick]], [[3icm\|3icm]], [[3icn\|3icn]], [[3icz\|3icz]], [[4dwb\|4dwb]], [[4dwg\|4dwg]], [[4dxj\|4dxj]], [[4dzw\|4dzw]]</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='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 TRYCR])</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=4e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e1e RCSB], [http://www.ebi.ac.uk/pdbsum/4e1e 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=4e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1e OCA], [http://pdbe.org/4e1e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e1e RCSB], [http://www.ebi.ac.uk/pdbsum/4e1e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e1e ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 17:		Line 18:
	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 4e1e" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Trypanosoma cruzi~~]]		[[Category: Trycr]]
	[[Category: Amzel, L M]]		[[Category: Amzel, L M]]
	[[Category: Aripirala, S]]		[[Category: Aripirala, S]]

OCA at 14:32, 4 January 2015

2015-01-04T14:32:40Z

← Older revision		Revision as of 14:32, 4 January 2015
Line 1:		Line 1:
	~~{{STRUCTURE_4e1e\| PDB=4e1e \| SCENE= }}~~		==Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+==
	===Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+===		<StructureSection load='4e1e' size='340' side='right' caption='[[4e1e]], [[Resolution\|resolution]] 2.65Å' scene=''>
	~~{{ABSTRACT_PUBMED_22715997}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4e1e]] 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=4E1E OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E1E FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0MW:[2-(HEXYLAMINO)ETHANE-1,1-DIYL]BIS(PHOSPHONIC+ACID)'>0MW</scene>, <scene name='pdbligand=IPE:3-METHYLBUT-3-ENYL+TRIHYDROGEN+DIPHOSPHATE'>IPE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1yhk\|1yhk]], [[1yhl\|1yhl]], [[1yhm\|1yhm]], [[3iba\|3iba]], [[3ick\|3ick]], [[3icm\|3icm]], [[3icn\|3icn]], [[3icz\|3icz]], [[4dwb\|4dwb]], [[4dwg\|4dwg]], [[4dxj\|4dxj]], [[4dzw\|4dzw]]</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=4e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e1e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e1e RCSB], [http://www.ebi.ac.uk/pdbsum/4e1e PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Linear 2-alkylaminoethyl-1,1-bisphosphonates are effective agents against proliferation of Trypanosoma cruzi , the etiologic agent of American trypanosomiasis (Chagas disease), exhibiting IC(50) values in the nanomolar range against the parasites. This activity is associated with inhibition at the low nanomolar level of the T. cruzi farnesyl diphosphate synthase (TcFPPS). X-ray structures and thermodynamic data of the complexes TcFPPS with five compounds of this family show that the inhibitors bind to the allylic site of the enzyme, with their alkyl chain occupying the cavity that binds the isoprenoid chain of the substrate. The compounds bind to TcFPPS with unfavorable enthalpy compensated by a favorable entropy that results from a delicate balance between two opposing effects: the loss of conformational entropy due to freezing of single bond rotations and the favorable burial of the hydrophobic alkyl chains. The data suggest that introduction of strategically placed double bonds and methyl branches should increase affinity substantially.

	~~==About this Structure==~~		Design, synthesis, calorimetry, and crystallographic analysis of 2-alkylaminoethyl-1,1-bisphosphonates as inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase.,Aripirala S, Szajnman SH, Jakoncic J, Rodriguez JB, Docampo R, Gabelli SB, Amzel LM J Med Chem. 2012 Jul 26;55(14):6445-54. Epub 2012 Jul 5. PMID:22715997<ref>PMID:22715997</ref>
	~~[[4e1e]] 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~~=~~4E1E OCA~~].
			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

			==See Also==
			*[[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: Aripirala, S.]]		[[Category: Aripirala, S]]
	[[Category: Gabelli, S B.]]		[[Category: Gabelli, S B]]
	[[Category: Farnesyl pyrophosphate synthase]]		[[Category: Farnesyl pyrophosphate synthase]]
	[[Category: Geranyl transferase]]		[[Category: Geranyl transferase]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 19:30, 17 April 2013

2013-04-17T19:30:22Z

← Older revision		Revision as of 19:30, 17 April 2013
Line 1:		Line 1:
	~~[[Image:4e1e.jpg\|left\|200px]]~~

	{{STRUCTURE_4e1e\| PDB=4e1e \| SCENE= }}		{{STRUCTURE_4e1e\| PDB=4e1e \| SCENE= }}

	===Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+===		===Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+===

	{{ABSTRACT_PUBMED_22715997}}		{{ABSTRACT_PUBMED_22715997}}

	==About this Structure==		==About this Structure==
	[[4e1e]] 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=4E1E OCA].		[[4e1e]] 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=4E1E OCA].
	~~[[Category: Geranyltranstransferase]]~~
	[[Category: Trypanosoma cruzi]]		[[Category: Trypanosoma cruzi]]
	[[Category: Amzel, L M.]]		[[Category: Amzel, L M.]]

OCA at 08:59, 16 January 2013

2013-01-16T08:59:34Z

← Older revision		Revision as of 08:59, 16 January 2013
Line 1:		Line 1:
	~~'''Unreleased structure'''~~		[[Image:4e1e.jpg\|left\|200px]]

	~~The entry~~ 4e1e ~~is ON HOLD~~ ~~until Paper Publication~~		{{STRUCTURE_4e1e\| PDB=4e1e \| SCENE= }}

	~~Authors: Aripirala~~, ~~S., Amzel, L.M., Gabelli, S.B.~~		===Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+===

	~~Description~~: ~~Crystal structure of Trypanosome~~ cruzi ~~farnesyl diphosphate synthase in complex with~~ [2-~~(n-hexylamino)ethane-1~~,1-~~diyl~~]~~bisphosphonic acid and Mg2+~~		{{ABSTRACT_PUBMED_22715997}}

			==About this Structure==
			[[4e1e]] 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=4E1E OCA].
			[[Category: Geranyltranstransferase]]
			[[Category: Trypanosoma cruzi]]
			[[Category: Amzel, L M.]]
			[[Category: Aripirala, S.]]
			[[Category: Gabelli, S B.]]
			[[Category: Farnesyl pyrophosphate synthase]]
			[[Category: Geranyl transferase]]
			[[Category: Transferase-transferase inhibitor complex]]

OCA at 05:35, 23 May 2012

2012-05-23T05:35:14Z

← Older revision		Revision as of 05:35, 23 May 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4e1e is ON HOLD		The entry 4e1e is ON HOLD until Paper Publication

	Authors: Aripirala, S., Amzel, L.M., Gabelli, S.B.		Authors: Aripirala, S., Amzel, L.M., Gabelli, S.B.

	Description: Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+		Description: Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+

OCA: Protected "4e1e" [edit=sysop:move=sysop]

2012-03-14T06:15:55Z

Protected "4e1e" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:15, 14 March 2012
(No difference)

OCA: New page: '''Unreleased structure''' The entry 4e1e is ON HOLD Authors: Aripirala, S., Amzel, L.M., Gabelli, S.B. Description: Crystal structure of Trypanosome cruzi farnesyl diphosphate synthas...

2012-03-14T06:15:54Z

New page: '''Unreleased structure''' The entry 4e1e is ON HOLD Authors: Aripirala, S., Amzel, L.M., Gabelli, S.B. Description: Crystal structure of Trypanosome cruzi farnesyl diphosphate synthas...

New page

'''Unreleased structure'''

The entry 4e1e is ON HOLD

Authors: Aripirala, S., Amzel, L.M., Gabelli, S.B.

Description: Crystal structure of Trypanosome cruzi farnesyl diphosphate synthase in complex with [2-(n-hexylamino)ethane-1,1-diyl]bisphosphonic acid and Mg2+