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3qv6

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==Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with acid blue 80.==
==Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with acid blue 80.==
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<StructureSection load='3qv6' size='340' side='right' caption='[[3qv6]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
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<StructureSection load='3qv6' size='340' side='right'caption='[[3qv6]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3qv6]] is a 2 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=3QV6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QV6 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3qv6]] is a 2 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=3QV6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QV6 FirstGlance]. <br>
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</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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QV6:3-({4-[(2,4-DIMETHYL-5-SULFOPHENYL)AMINO]-9,10-DIOXO-9,10-DIHYDROANTHRACEN-1-YL}AMINO)-2,4,6-TRIMETHYLBENZENESULFONIC+ACID'>QV6</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.85&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pkl|1pkl]], [[3qv7|3qv7]], [[3qv8|3qv8]], [[3qv9|3qv9]]</td></tr>
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<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=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=QV6:3-({4-[(2,4-DIMETHYL-5-SULFOPHENYL)AMINO]-9,10-DIOXO-9,10-DIHYDROANTHRACEN-1-YL}AMINO)-2,4,6-TRIMETHYLBENZENESULFONIC+ACID'>QV6</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PYK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5665 LEIME])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3qv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv6 OCA], [https://pdbe.org/3qv6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qv6 RCSB], [https://www.ebi.ac.uk/pdbsum/3qv6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qv6 ProSAT]</span></td></tr>
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<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>
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<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=3qv6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qv6 OCA], [http://pdbe.org/3qv6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qv6 RCSB], [http://www.ebi.ac.uk/pdbsum/3qv6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qv6 ProSAT]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/KPYK_LEIME KPYK_LEIME]
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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.
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3qv6" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
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*[[Pyruvate Kinase|Pyruvate Kinase]]
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*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Leime]]
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[[Category: Large Structures]]
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[[Category: Pyruvate kinase]]
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[[Category: Leishmania mexicana]]
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[[Category: Auld, D S]]
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[[Category: Auld DS]]
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[[Category: Fothergill-Gilmore, L A]]
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[[Category: Fothergill-Gilmore LA]]
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[[Category: McNae, I W]]
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[[Category: McNae IW]]
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[[Category: Michels, P A.M]]
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[[Category: Michels PAM]]
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[[Category: Morgan, H P]]
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[[Category: Morgan HP]]
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[[Category: Nowicki, M W]]
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[[Category: Nowicki MW]]
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[[Category: Walkinshaw, M D]]
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[[Category: Walkinshaw MD]]
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[[Category: Adp/atp binding]]
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[[Category: Cytosol]]
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[[Category: Glycolysis]]
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[[Category: Sugar kinase]]
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[[Category: Tim barrel]]
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[[Category: Transferase-transferase inhibitor complex]]
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Current revision

Crystal structure of Leishmania mexicana pyruvate kinase(LmPYK)in complex with acid blue 80.

PDB ID 3qv6

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