8iax: Difference between revisions

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-'''Unreleased structure'''
-The entry 8iax is ON HOLD
+==Crystal structure of Streptococcus pneumoniae pyruvate kinase in complex with phosphoenolpyruvate and fructose 1,6-bisphosphate==
+<StructureSection load='8iax' size='340' side='right'caption='[[8iax]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8iax]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8IAX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IAX 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]] 1.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBP:BETA-FRUCTOSE-1,6-DIPHOSPHATE'>FBP</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8iax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8iax OCA], [https://pdbe.org/8iax PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8iax RCSB], [https://www.ebi.ac.uk/pdbsum/8iax PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8iax ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q8DQ84_STRR6 Q8DQ84_STRR6]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Glycolysis is the primary metabolic pathway in the strictly fermentative Streptococcus pneumoniae, which is a major human pathogen associated with antibiotic resistance. Pyruvate kinase (PYK) is the last enzyme in this pathway that catalyzes the production of pyruvate from phosphoenolpyruvate (PEP) and plays a crucial role in controlling carbon flux; however, while S. pneumoniae PYK (SpPYK) is indispensable for growth, surprisingly little is known about its functional properties. Here, we report that compromising mutations in SpPYK confers resistance to the antibiotic fosfomycin, which inhibits the peptidoglycan synthesis enzyme MurA, implying a direct link between PYK and cell wall biogenesis. The crystal structures of SpPYK in the apo and ligand-bound states reveal key interactions that contribute to its conformational change as well as residues responsible for the recognition of PEP and the allosteric activator fructose 1,6-bisphosphate (FBP). Strikingly, FBP binding was observed at a location distinct from previously reported PYK effector binding sites. Furthermore, we show that SpPYK could be engineered to become more responsive to glucose 6-phosphate instead of FBP by sequence and structure-guided mutagenesis of the effector binding site. Together, our work sheds light on the regulatory mechanism of SpPYK and lays the groundwork for antibiotic development that targets this essential enzyme.
-Authors: Nakashima, R., Taguchi, A.
+Functional and structural characterization of Streptococcus pneumoniae pyruvate kinase involved in fosfomycin resistance.,Taguchi A, Nakashima R, Nishino K J Biol Chem. 2023 Jul;299(7):104892. doi: 10.1016/j.jbc.2023.104892. Epub 2023 , Jun 5. PMID:37286036<ref>PMID:37286036</ref>
-Description: Crystal structure of Streptococcus pneumoniae pyruvate kinase in complex with phosphoenolpyruvate and fructose 1,6-bisphosphate
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Taguchi, A]]
+<div class="pdbe-citations 8iax" style="background-color:#fffaf0;"></div>
-[[Category: Nakashima, R]]
+==See Also==
+*[[Pyruvate kinase 3D structures|Pyruvate kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Streptococcus pneumoniae R6]]
+[[Category: Nakashima R]]
+[[Category: Taguchi A]]