8iax | pdb_00008iax

Crystal structure of Streptococcus pneumoniae pyruvate kinase in complex with phosphoenolpyruvate and fructose 1,6-bisphosphate

spinqualitylabelsall models 8iax, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8iax is a 8 chain structure with sequence from Streptococcus pneumoniae R6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: FBP, K, MG, PEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8DQ84_STRR6 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyruvate kinase 3D structures

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