8XW7

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

8XW7 の概要

• エントリーDOI: 10.2210/pdb8xw7/pdb
• 分子名称: Pyruvate kinase, MAGNESIUM ION, POTASSIUM ION, ... (8 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: 2
• 化学式量合計: 115965.36

構造登録者

Nakashima, R.,Taguchi, A. (登録日: 2024-01-16, 公開日: 2024-07-31, 最終更新日: 2024-08-07)

主引用文献

Taguchi, A.,Nakashima, R.,Nishino, K.
Structural Basis of Nucleotide Selectivity in Pyruvate Kinase.
J.Mol.Biol., 436:168708-168708, 2024

PubMed Abstract: Nucleoside triphosphates are indispensable in numerous biological processes, with enzymes involved in their biogenesis playing pivotal roles in cell proliferation. Pyruvate kinase (PYK), commonly regarded as the terminal glycolytic enzyme that generates ATP in tandem with pyruvate, is also capable of synthesizing a wide range of nucleoside triphosphates from their diphosphate precursors. Despite their substrate promiscuity, some PYKs show preference towards specific nucleotides, suggesting an underlying mechanism for differentiating nucleotide bases. However, the thorough characterization of this mechanism has been hindered by the paucity of nucleotide-bound PYK structures. Here, we present crystal structures of Streptococcus pneumoniae PYK in complex with four different nucleotides. These structures facilitate direct comparison of the protein-nucleotide interactions and offer structural insights into its pronounced selectivity for GTP synthesis. Notably, this selectivity is dependent on a sequence motif in the nucleotide recognition site that is widely present among prokaryotic PYKs, particularly in Firmicutes species. We show that pneumococcal cell growth is significantly impaired when expressing a PYK variant with compromised GTP and UTP synthesis activity, underscoring the importance of PYK in maintaining nucleotide homeostasis. Our findings collectively advance our understanding of PYK biochemistry and prokaryotic metabolism.

PubMed: 39009072
DOI: 10.1016/j.jmb.2024.168708

実験手法

X-RAY DIFFRACTION (2.1 Å)