View source for 1pkl


==THE STRUCTURE OF LEISHMANIA PYRUVATE KINASE==
<StructureSection load='1pkl' size='340' side='right'caption='[[1pkl]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1pkl]] is a 8 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=1PKL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PKL 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]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=1pkl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pkl OCA], [https://pdbe.org/1pkl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pkl RCSB], [https://www.ebi.ac.uk/pdbsum/1pkl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pkl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KPYK_LEIME KPYK_LEIME] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pk/1pkl_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pkl ConSurf].
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== Publication Abstract from PubMed ==
Glycolysis occupies a central role in cellular metabolism, and is of particular importance for the catabolic production of ATP in protozoan parasites such as Leishmania and Trypanosoma. In these organisms pyruvate kinase plays a key regulatory role, and is unique in responding to fructose 2,6-bisphosphate as allosteric activator. The determination of the first eukaryotic pyruvate kinase crystal structure in the T-state is reported. A comparison of the leishmania and yeast R-state enzymes reveals fewer differences than the previous comparison of Escherichia coli T-state and rabbit muscle non-allosteric enzymes. Structural changes related to the allosteric transition can therefore be distinguished from those that are a consequence of the inherent wide structural divergence between bacterial and mammalian proteins. The allosteric transition involves significant changes in a tightly packed array of eight alpha helices at the interface near the catalytic site. At the other interface the allosteric transition appears to be accompanied by the bending of a ten-stranded intersubunit beta sheet adjacent to the effector site. Helix Calpha1 makes contacts to the N-terminal helical domain and bridges both interfaces. A comparison of the effector sites of the leishmania and yeast enzymes reveals the structural basis for the different effector specificity. Two loops comprising residues 443-453 and 480-489 adopt very different conformations in the two enzymes, and Lys453 and His480 that are a feature of trypanosomatid enzymes provide probable ligands for the 2-phospho group of the effector molecule. These differences offer an opportunity for the design of drugs that would bind to the trypanosomatid enzymes but not to those of the mammalian host.

The structure of pyruvate kinase from Leishmania mexicana reveals details of the allosteric transition and unusual effector specificity.,Rigden DJ, Phillips SE, Michels PA, Fothergill-Gilmore LA J Mol Biol. 1999 Aug 20;291(3):615-35. PMID:10448041<ref>PMID:10448041</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1pkl" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Leishmania mexicana]]
[[Category: Fothergill-Gilmore LA]]
[[Category: Michels PAM]]
[[Category: Phillips SEV]]
[[Category: Rigden DJ]]