8IAV

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

8IAV の概要

• エントリーDOI: 10.2210/pdb8iav/pdb
• 関連するPDBエントリー: 8AIT 8AIU 8IAS
• 分子名称: Pyruvate kinase, 1,6-di-O-phosphono-beta-D-fructofuranose (3 entities in total)
• 機能のキーワード: pyruvate kinase, streptococcus pneumoniae, glycolysis, transferase
• 由来する生物種: Streptococcus pneumoniae R6
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 229334.82

構造登録者

Nakashima, R.,Taguchi, A. (登録日: 2023-02-09, 公開日: 2023-06-14, 最終更新日: 2024-05-29)

主引用文献

Taguchi, A.,Nakashima, R.,Nishino, K.
Functional and structural characterization of Streptococcus pneumoniae pyruvate kinase involved in fosfomycin resistance.
J.Biol.Chem., 299:104892-104892, 2023

PubMed Abstract: 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.

PubMed: 37286036
DOI: 10.1016/j.jbc.2023.104892

実験手法

X-RAY DIFFRACTION (2.59 Å)