3qv7 - Revision history

OCA at 11:59, 14 March 2024

2024-03-14T11:59:55Z

← Older revision		Revision as of 11:59, 14 March 2024
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	<StructureSection load='3qv7' size='340' side='right'caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='3qv7' size='340' side='right'caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Leime Leime~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QV7:3-HYDROXY-4-[(E)-{2-SULFO-4-[(E)-(4-SULFOPHENYL)DIAZENYL]PHENYL}DIAZENYL]NAPHTHALENE-2,7-DISULFONIC+ACID'>QV7</scene>, <scene name='pdbligand=QV8:9,10-DIOXO-4-(PHENYLAMINO)-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>QV8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.7Å</td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pkl\|1pkl]], [[3qv6\|3qv6]], [[3qv8\|3qv8]], [[3qv9\|3qv9]]</div></td></tr>		<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QV7:3-HYDROXY-4-[(E)-{2-SULFO-4-[(E)-(4-SULFOPHENYL)DIAZENYL]PHENYL}DIAZENYL]NAPHTHALENE-2,7-DISULFONIC+ACID'>QV7</scene>, <scene name='pdbligand=QV8:9,10-DIOXO-4-(PHENYLAMINO)-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>QV8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PKY ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 LEIME])</td></tr>~~
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </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=3qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv7 OCA], [https://pdbe.org/3qv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qv7 RCSB], [https://www.ebi.ac.uk/pdbsum/3qv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qv7 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=3qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv7 OCA], [https://pdbe.org/3qv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qv7 RCSB], [https://www.ebi.ac.uk/pdbsum/3qv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qv7 ProSAT]</span></td></tr>
	</table>		</table>
	~~<div style~~=~~"background-color:#fffaf0;">~~		== Function ==
	=~~= Publication Abstract from PubMed~~ ==		[https://www.uniprot.org/uniprot/KPYK_LEIME KPYK_LEIME]
	Ehrlich's pioneering chemotherapeutic experiments published in 1904 described the efficacy of a series of dye molecules including trypan blue and trypan red to eliminate trypanosome infections in mice. The molecular structures of the dyes provided a starting point for the synthesis of suramin which was developed and used as a trypanocidal drug in 1916, and is still in clinical use. Despite the biological importance of these dye-like molecules, the mode of action on trypanosomes has remained elusive. Here we present crystal structures of suramin and three related dyes in complex with pyruvate kinases from Leishmania mexicana or from Trypanosoma cruzi. The phenyl sulfonate groups of all four molecules (suramin, Ponceau S, acid blue 80 and benzothiazole-2,5-disulfonic acid) bind in the position of ADP/ATP at the active sites of the PYKs. The binding positions in the two different trypanosomatid PYKs are nearly identical. We show that suramin competitively inhibits PYKs from humans (muscle, tumor and liver isoenzymes, Ki = 1.1 to 17 muM), T. cruzi (Ki = 108 muM) and L. mexicana (Ki = 116 muM), all of which have similar active sites. Synergistic effects were observed when examining suramin inhibition in the presence of an allosteric effector molecule, whereby IC50 values decreased up to two-fold for both trypanosomatid and human PYKs. These kinetic and structural analyses provide insight into the promiscuous inhibition observed for suramin, and into the mode of action of the dye-like molecules used in Ehrlich's original experiments.

	The trypanocidal drug suramin and other trypan blue mimetics are inhibitors of pyruvate kinases and bind to the adenosine site.,Morgan HP, McNae IW, Nowicki MW, Zhong W, Michels PA, Auld DS, Fothergill-Gilmore LA, Walkinshaw MD J Biol Chem. 2011 Jul 5. PMID:21733839<ref>PMID:~~21733839<~~/~~ref>~~

	~~From MEDLINE®~~/~~PubMed®, a database of the U.S~~. ~~National Library of Medicine~~.~~<br>~~
	</~~div>~~
	~~<div class="pdbe-citations 3qv7" style="background-color:#fffaf0;"><~~/~~div>~~

	==See Also==		==See Also==
	*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]		*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Leime]]~~		[[Category: Leishmania mexicana]]
	~~[[Category: Pyruvate kinase~~]]		[[Category: Auld DS]]
	[[Category: Auld~~, D S~~]]		[[Category: Fothergill-Gilmore LA]]
	[[Category: Fothergill-Gilmore~~, L A~~]]		[[Category: McNae IW]]
	[[Category: McNae~~, I W~~]]		[[Category: Michels PAM]]
	[[Category: Michels~~, P A.M~~]]		[[Category: Morgan HP]]
	[[Category: Morgan~~, H P~~]]		[[Category: Nowicki MW]]
	[[Category: Nowicki~~, M W~~]]		[[Category: Walkinshaw MD]]
	[[Category: Walkinshaw~~, M D]]~~
	~~[[Category: Adp/atp binding]]~~
	~~[[Category: Cytosol]]~~
	~~[[Category: Glycolysis]]~~
	~~[[Category: Sugar kinase]]~~
	~~[[Category: Tim barrel]]~~
	~~[[Category: Transferase-transferase inhibitor complex~~]]

OCA at 05:37, 15 June 2022

2022-06-15T05:37:39Z

← Older revision		Revision as of 05:37, 15 June 2022
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	<StructureSection load='3qv7' size='340' side='right'caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='3qv7' size='340' side='right'caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Leime Leime]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Leime Leime]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QV7:3-HYDROXY-4-[(E)-{2-SULFO-4-[(E)-(4-SULFOPHENYL)DIAZENYL]PHENYL}DIAZENYL]NAPHTHALENE-2,7-DISULFONIC+ACID'>QV7</scene>, <scene name='pdbligand=QV8:9,10-DIOXO-4-(PHENYLAMINO)-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>QV8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QV7:3-HYDROXY-4-[(E)-{2-SULFO-4-[(E)-(4-SULFOPHENYL)DIAZENYL]PHENYL}DIAZENYL]NAPHTHALENE-2,7-DISULFONIC+ACID'>QV7</scene>, <scene name='pdbligand=QV8:9,10-DIOXO-4-(PHENYLAMINO)-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>QV8</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">[[1pkl\|1pkl]], [[3qv6\|3qv6]], [[3qv8\|3qv8]], [[3qv9\|3qv9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pkl\|1pkl]], [[3qv6\|3qv6]], [[3qv8\|3qv8]], [[3qv9\|3qv9]]</div></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PKY ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 LEIME])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PKY ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 LEIME])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </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=3qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv7 OCA], [~~http~~://pdbe.org/3qv7 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3qv7 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3qv7 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3qv7 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=3qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv7 OCA], [https://pdbe.org/3qv7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qv7 RCSB], [https://www.ebi.ac.uk/pdbsum/3qv7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qv7 ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">

OCA at 15:51, 29 January 2020

2020-01-29T15:51:04Z

← Older revision		Revision as of 15:51, 29 January 2020
Line 1:		Line 1:

	==Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.==		==Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.==
	<StructureSection load='3qv7' size='340' side='right' caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='3qv7' size='340' side='right'caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leime Leime]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leime Leime]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>
Line 21:		Line 21:

	==See Also==		==See Also==
	*[[Pyruvate ~~Kinase~~\|Pyruvate ~~Kinase~~]]		*[[Pyruvate kinase 3D structures\|Pyruvate kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Large Structures]]
	[[Category: Leime]]		[[Category: Leime]]
	[[Category: Pyruvate kinase]]		[[Category: Pyruvate kinase]]

OCA at 11:59, 5 August 2016

2016-08-05T11:59:18Z

← Older revision		Revision as of 11:59, 5 August 2016
Line 1:		Line 1:

	==Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.==		==Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.==
	<StructureSection load='3qv7' size='340' side='right' caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='3qv7' size='340' side='right' caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Leishmania_mexicana Leishmania mexicana~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>		<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leime Leime]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QV7:3-HYDROXY-4-[(E)-{2-SULFO-4-[(E)-(4-SULFOPHENYL)DIAZENYL]PHENYL}DIAZENYL]NAPHTHALENE-2,7-DISULFONIC+ACID'>QV7</scene>, <scene name='pdbligand=QV8:9,10-DIOXO-4-(PHENYLAMINO)-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>QV8</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QV7:3-HYDROXY-4-[(E)-{2-SULFO-4-[(E)-(4-SULFOPHENYL)DIAZENYL]PHENYL}DIAZENYL]NAPHTHALENE-2,7-DISULFONIC+ACID'>QV7</scene>, <scene name='pdbligand=QV8:9,10-DIOXO-4-(PHENYLAMINO)-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>QV8</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">[[1pkl\|1pkl]], [[3qv6\|3qv6]], [[3qv8\|3qv8]], [[3qv9\|3qv9]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1pkl\|1pkl]], [[3qv6\|3qv6]], [[3qv8\|3qv8]], [[3qv9\|3qv9]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PKY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 ~~Leishmania mexicana~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PKY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 LEIME])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </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=3qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qv7 RCSB], [http://www.ebi.ac.uk/pdbsum/3qv7 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=3qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv7 OCA], [http://pdbe.org/3qv7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qv7 RCSB], [http://www.ebi.ac.uk/pdbsum/3qv7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qv7 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 3qv7" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 24:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Leishmania mexicana~~]]		[[Category: Leime]]
	[[Category: Pyruvate kinase]]		[[Category: Pyruvate kinase]]
	[[Category: Auld, D S]]		[[Category: Auld, D S]]

OCA at 08:23, 18 December 2014

2014-12-18T08:23:59Z

← Older revision		Revision as of 08:23, 18 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_3qv7\| PDB=3qv7 \| SCENE= }}~~		==Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.==
	===Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.===		<StructureSection load='3qv7' size='340' side='right' caption='[[3qv7]], [[Resolution\|resolution]] 2.70Å' scene=''>
	{~~{ABSTRACT_PUBMED_21733839}~~}		== Structural highlights ==
			<table><tr><td colspan='2'>[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QV7 FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=QV7:3-HYDROXY-4-[(E)-{2-SULFO-4-[(E)-(4-SULFOPHENYL)DIAZENYL]PHENYL}DIAZENYL]NAPHTHALENE-2,7-DISULFONIC+ACID'>QV7</scene>, <scene name='pdbligand=QV8:9,10-DIOXO-4-(PHENYLAMINO)-9,10-DIHYDROANTHRACENE-2-SULFONIC+ACID'>QV8</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">[[1pkl\|1pkl]], [[3qv6\|3qv6]], [[3qv8\|3qv8]], [[3qv9\|3qv9]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">PKY ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 Leishmania mexicana])</td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pyruvate_kinase Pyruvate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.40 2.7.1.40] </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=3qv7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qv7 RCSB], [http://www.ebi.ac.uk/pdbsum/3qv7 PDBsum]</span></td></tr>
			</table>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Ehrlich's pioneering chemotherapeutic experiments published in 1904 described the efficacy of a series of dye molecules including trypan blue and trypan red to eliminate trypanosome infections in mice. The molecular structures of the dyes provided a starting point for the synthesis of suramin which was developed and used as a trypanocidal drug in 1916, and is still in clinical use. Despite the biological importance of these dye-like molecules, the mode of action on trypanosomes has remained elusive. Here we present crystal structures of suramin and three related dyes in complex with pyruvate kinases from Leishmania mexicana or from Trypanosoma cruzi. The phenyl sulfonate groups of all four molecules (suramin, Ponceau S, acid blue 80 and benzothiazole-2,5-disulfonic acid) bind in the position of ADP/ATP at the active sites of the PYKs. The binding positions in the two different trypanosomatid PYKs are nearly identical. We show that suramin competitively inhibits PYKs from humans (muscle, tumor and liver isoenzymes, Ki = 1.1 to 17 muM), T. cruzi (Ki = 108 muM) and L. mexicana (Ki = 116 muM), all of which have similar active sites. Synergistic effects were observed when examining suramin inhibition in the presence of an allosteric effector molecule, whereby IC50 values decreased up to two-fold for both trypanosomatid and human PYKs. These kinetic and structural analyses provide insight into the promiscuous inhibition observed for suramin, and into the mode of action of the dye-like molecules used in Ehrlich's original experiments.

	~~==About this Structure==~~		The trypanocidal drug suramin and other trypan blue mimetics are inhibitors of pyruvate kinases and bind to the adenosine site.,Morgan HP, McNae IW, Nowicki MW, Zhong W, Michels PA, Auld DS, Fothergill-Gilmore LA, Walkinshaw MD J Biol Chem. 2011 Jul 5. PMID:21733839<ref>PMID:21733839</ref>
	~~[[3qv7]] is a 4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Leishmania_mexicana Leishmania mexicana]~~. ~~Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.~~il/oca-bin~~/~~ocashort?id=3QV7 OCA].~~
			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>

	==See Also==		==See Also==
	*[[Pyruvate Kinase\|Pyruvate Kinase]]		*[[Pyruvate Kinase\|Pyruvate Kinase]]
			== References ==
	==~~Reference~~==		<references/>
	<~~ref group="xtra">PMID:021733839<~~/~~ref~~><~~references group="xtra"~~/>		__TOC__
			</StructureSection>
	[[Category: Leishmania mexicana]]		[[Category: Leishmania mexicana]]
	[[Category: Pyruvate kinase]]		[[Category: Pyruvate kinase]]
	[[Category: Auld, D S.]]		[[Category: Auld, D S]]
	[[Category: Fothergill-Gilmore, L A.]]		[[Category: Fothergill-Gilmore, L A]]
	[[Category: McNae, I W.]]		[[Category: McNae, I W]]
	[[Category: Michels, P A.M.]]		[[Category: Michels, P A.M]]
	[[Category: Morgan, H P.]]		[[Category: Morgan, H P]]
	[[Category: Nowicki, M W.]]		[[Category: Nowicki, M W]]
	[[Category: Walkinshaw, M D.]]		[[Category: Walkinshaw, M D]]
	[[Category: Adp/atp binding]]		[[Category: Adp/atp binding]]
	[[Category: Cytosol]]		[[Category: Cytosol]]
	[[Category: Glycolysis]]		[[Category: Glycolysis]]
	~~[[Category: Pyruvate kinase]]~~
	[[Category: Sugar kinase]]		[[Category: Sugar kinase]]
	[[Category: Tim barrel]]		[[Category: Tim barrel]]
	[[Category: Transferase-transferase inhibitor complex]]		[[Category: Transferase-transferase inhibitor complex]]

OCA at 10:50, 11 March 2013

2013-03-11T10:50:42Z

← Older revision		Revision as of 10:50, 11 March 2013
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	~~[[Image:3qv7.png\|left\|200px]]~~

	~~<!--~~
	~~The line below this paragraph, containing "STRUCTURE_3qv7", creates the "Structure Box" on the page.~~
	~~You may change the PDB parameter (which sets the PDB file loaded into the applet)~~
	~~or the SCENE parameter (which sets the initial scene displayed when the page is loaded),~~
	~~or leave the SCENE parameter empty for the default display.~~
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	{{STRUCTURE_3qv7\| PDB=3qv7 \| SCENE= }}		{{STRUCTURE_3qv7\| PDB=3qv7 \| SCENE= }}

	===Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.===		===Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.===


	~~<!--~~
	~~The line below this paragraph, {{ABSTRACT_PUBMED_21733839}}, adds the Publication Abstract to the page~~
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	==See Also==		==See Also==
	*[[Pyruvate Kinase]]		*[[Pyruvate Kinase\|Pyruvate Kinase]]

	==Reference==		==Reference==

OCA at 05:14, 24 August 2011

2011-08-24T05:14:31Z

← Older revision		Revision as of 05:14, 24 August 2011
Line 20:		Line 20:
	==About this Structure==		==About this Structure==
	[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA].		[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA].

			==See Also==
			*[[Pyruvate Kinase]]

	==Reference==		==Reference==

OCA at 06:41, 17 August 2011

2011-08-17T06:41:47Z

← Older revision		Revision as of 06:41, 17 August 2011
Line 25:		Line 25:
	[[Category: Leishmania mexicana]]		[[Category: Leishmania mexicana]]
	[[Category: Pyruvate kinase]]		[[Category: Pyruvate kinase]]
			[[Category: Auld, D S.]]
			[[Category: Fothergill-Gilmore, L A.]]
			[[Category: McNae, I W.]]
			[[Category: Michels, P A.M.]]
	[[Category: Morgan, H P.]]		[[Category: Morgan, H P.]]
			[[Category: Nowicki, M W.]]
	[[Category: Walkinshaw, M D.]]		[[Category: Walkinshaw, M D.]]
	[[Category: Adp/atp binding]]		[[Category: Adp/atp binding]]

OCA at 08:02, 3 August 2011

2011-08-03T08:02:42Z

← Older revision		Revision as of 08:02, 3 August 2011
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	[[Image:3qv7.~~jpg~~\|left\|200px]]		[[Image:3qv7.png\|left\|200px]]

	<!--		<!--
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	===Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.===		===Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.===


			<!--
			The line below this paragraph, {{ABSTRACT_PUBMED_21733839}}, adds the Publication Abstract to the page
			(as it appears on PubMed at http://www.pubmed.gov), where 21733839 is the PubMed ID number.
			-->
			{{ABSTRACT_PUBMED_21733839}}

	==About this Structure==		==About this Structure==
	[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA].		[[3qv7]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Leishmania_mexicana Leishmania mexicana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QV7 OCA].

			==Reference==
			<ref group="xtra">PMID:021733839</ref><references group="xtra"/>
	[[Category: Leishmania mexicana]]		[[Category: Leishmania mexicana]]
	[[Category: Pyruvate kinase]]		[[Category: Pyruvate kinase]]

OCA at 06:21, 29 June 2011

2011-06-29T06:21:23Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+[[Image:3qv7.jpg|left|200px]]
-The entry 3qv7 is ON HOLD  until Paper Publication
+<!--
-Authors: Morgan, H.P., Walkinshaw, M.D.
+===Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.===
-Description: Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with ponceau S and acid blue 25.