6nn4
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6nn4 is ON HOLD until Paper Publication Authors: McFarlane, J.S., Ronnebaum, T.A., Meneely, K.M., Fenton, A.W., Lamb, A.L. Description: The structu...) |
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The structure of human liver pyruvate kinase, hLPYK-D499N, in complex with Fru-1,6-BP== |
| + | <StructureSection load='6nn4' size='340' side='right'caption='[[6nn4]], [[Resolution|resolution]] 2.15Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6nn4]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NN4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NN4 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]] 2.15Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=PEP:PHOSPHOENOLPYRUVATE'>PEP</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=6nn4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nn4 OCA], [https://pdbe.org/6nn4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nn4 RCSB], [https://www.ebi.ac.uk/pdbsum/6nn4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nn4 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Defects in PKLR are the cause of pyruvate kinase hyperactivity (PKHYP) [MIM:[https://omim.org/entry/102900 102900]; also known as high red cell ATP syndrome. This autosomal dominant phenotype is characterized by increase of red blood cell ATP.<ref>PMID:9090535</ref> Defects in PKLR are the cause of pyruvate kinase deficiency of red cells (PKRD) [MIM:[https://omim.org/entry/266200 266200]. A frequent cause of hereditary non-spherocytic hemolytic anemia. Clinically, pyruvate kinase-deficient patients suffer from a highly variable degree of chronic hemolysis, ranging from severe neonatal jaundice and fatal anemia at birth, severe transfusion-dependent chronic hemolysis, moderate hemolysis with exacerbation during infection, to a fully compensated hemolysis without apparent anemia. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/KPYR_HUMAN KPYR_HUMAN] Plays a key role in glycolysis (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human liver pyruvate kinase (hLPYK) converts phosphoenolpyruvate to pyruvate in the final step of glycolysis. hLPYK is allosterically activated by fructose-1,6-bisphosphate (Fru-1,6-BP). The allosteric site, as defined by previous structural studies, is located in domain C between the phosphate-binding loop (residues 444-449) and the allosteric loop (residues 527-533). In this study, the X-ray crystal structures of four hLPYK variants were solved to make structural correlations with existing functional data. The variants are D499N, W527H, Delta529/S531G (called GGG here) and S531E. The results revealed a conformational toggle between the open and closed positions of the allosteric loop. In the absence of Fru-1,6-BP the open position is stabilized, in part, by a cation-pi bond between Trp527 and Arg538' (from an adjacent monomer). In the S531E variant glutamate binds in place of the 6'-phosphate of Fru-1,6-BP in the allosteric site, leading to partial allosteric activation. Finally, the structure of the D499N mutant does not provide structural evidence for the previously observed allosteric activation of the D499N variant. | ||
| - | + | Changes in the allosteric site of human liver pyruvate kinase upon activator binding include the breakage of an intersubunit cation-pi bond.,McFarlane JS, Ronnebaum TA, Meneely KM, Chilton A, Fenton AW, Lamb AL Acta Crystallogr F Struct Biol Commun. 2019 Jun 1;75(Pt 6):461-469. doi:, 10.1107/S2053230X19007209. Epub 2019 Jun 10. PMID:31204694<ref>PMID:31204694</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Fenton | + | <div class="pdbe-citations 6nn4" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: Meneely | + | *[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]] |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Fenton AW]] | ||
| + | [[Category: Lamb AL]] | ||
| + | [[Category: McFarlane JS]] | ||
| + | [[Category: Meneely KM]] | ||
| + | [[Category: Ronnebaum TA]] | ||
Current revision
The structure of human liver pyruvate kinase, hLPYK-D499N, in complex with Fru-1,6-BP
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