6ksh: Difference between revisions
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==Crystal structure of pyruvate kinase (PYK) from Plasmodium falciparum in complex with oxalate and ATP== | |||
<StructureSection load='6ksh' size='340' side='right'caption='[[6ksh]], [[Resolution|resolution]] 2.60Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6ksh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KSH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KSH FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=OXL:OXALATE+ION'>OXL</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=6ksh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ksh OCA], [https://pdbe.org/6ksh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ksh RCSB], [https://www.ebi.ac.uk/pdbsum/6ksh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ksh ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C6KTA4_PLAF7 C6KTA4_PLAF7] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
During its intra-erythrocytic growth phase, the malaria parasite Plasmodium falciparum relies heavily on glycolysis for its energy requirements. Pyruvate kinase (PYK) is essential for regulating glycolytic flux and for ATP production, yet the allosteric mechanism of P. falciparum PYK (PfPYK) remains poorly understood. Here we report the first crystal structure of PfPYK in complex with substrate analogues oxalate and the ATP product. Comparisons of PfPYK structures in the active R-state and inactive T-state reveal a 'rock-and-lock' allosteric mechanism regulated by rigid-body rotations of each subunit in the tetramer. Kinetic data and structural analysis indicate glucose 6-phosphate is an activator by increasing the apparent maximal velocity of the enzyme. Intriguingly, the trypanosome drug suramin inhibits PfPYK, which points to glycolysis as a set of potential therapeutic targets against malaria. | |||
Pyruvate kinase from Plasmodium falciparum: Structural and kinetic insights into the allosteric mechanism.,Zhong W, Li K, Cai Q, Guo J, Yuan M, Wong YH, Walkinshaw MD, Fothergill-Gilmore LA, Michels PAM, Dedon PC, Lescar J Biochem Biophys Res Commun. 2020 Aug 30. pii: S0006-291X(20)31645-4. doi:, 10.1016/j.bbrc.2020.08.048. PMID:32878705<ref>PMID:32878705</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Cai | <div class="pdbe-citations 6ksh" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]] | ||
[[Category: Zhong | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Plasmodium falciparum 3D7]] | |||
[[Category: Cai Q]] | |||
[[Category: Dedon PC]] | |||
[[Category: Lescar J]] | |||
[[Category: Li K]] | |||
[[Category: Zhong W]] | |||
Latest revision as of 13:42, 22 November 2023
Crystal structure of pyruvate kinase (PYK) from Plasmodium falciparum in complex with oxalate and ATPCrystal structure of pyruvate kinase (PYK) from Plasmodium falciparum in complex with oxalate and ATP
Structural highlights
FunctionPublication Abstract from PubMedDuring its intra-erythrocytic growth phase, the malaria parasite Plasmodium falciparum relies heavily on glycolysis for its energy requirements. Pyruvate kinase (PYK) is essential for regulating glycolytic flux and for ATP production, yet the allosteric mechanism of P. falciparum PYK (PfPYK) remains poorly understood. Here we report the first crystal structure of PfPYK in complex with substrate analogues oxalate and the ATP product. Comparisons of PfPYK structures in the active R-state and inactive T-state reveal a 'rock-and-lock' allosteric mechanism regulated by rigid-body rotations of each subunit in the tetramer. Kinetic data and structural analysis indicate glucose 6-phosphate is an activator by increasing the apparent maximal velocity of the enzyme. Intriguingly, the trypanosome drug suramin inhibits PfPYK, which points to glycolysis as a set of potential therapeutic targets against malaria. Pyruvate kinase from Plasmodium falciparum: Structural and kinetic insights into the allosteric mechanism.,Zhong W, Li K, Cai Q, Guo J, Yuan M, Wong YH, Walkinshaw MD, Fothergill-Gilmore LA, Michels PAM, Dedon PC, Lescar J Biochem Biophys Res Commun. 2020 Aug 30. pii: S0006-291X(20)31645-4. doi:, 10.1016/j.bbrc.2020.08.048. PMID:32878705[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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