7Z4M

Plasmodium falciparum pyruvate kinase complexed with Mg2+ and K+

7Z4M の概要

• エントリーDOI: 10.2210/pdb7z4m/pdb
• 関連するPDBエントリー: 7Z4N 7Z4Q 7Z4R
• 分子名称: Pyruvate kinase, MAGNESIUM ION, POTASSIUM ION, ... (6 entities in total)
• 機能のキーワード: redox regulation, glycolysis, malaria, drug-target, transferase
• 由来する生物種: Plasmodium falciparum 3D7
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57261.74

構造登録者

Dillenberger, M.,Rahlfs, S.,Becker, K.,Fritz-Wolf, K. (登録日: 2022-03-04, 公開日: 2022-08-24, 最終更新日: 2024-01-31)

主引用文献

Dillenberger, M.,Rahlfs, S.,Becker, K.,Fritz-Wolf, K.
Prominent role of cysteine residues C49 and C343 in regulating Plasmodium falciparum pyruvate kinase activity.
Structure, 30:1452-, 2022

PubMed Abstract: The protozoan parasite Plasmodium falciparum causes the most severe form of malaria and is highly dependent on glycolysis. Glycolytic enzymes were shown to be massively redox regulated, inter alia via oxidative post-translational modifications (oxPTMs) of their cysteine residues. In this study, we identified P. falciparum pyruvate kinase (PfPK) C49 and C343 as amino acid residues essentially involved in maintaining structural and functional integrity of the enzyme. The mutation of these cysteines resulted in an altered substrate affinity, lower enzymatic activities, and, as studied by X-ray crystallography, conformational changes within the A-domain where the substrate binding site is located. Although the loss of a cysteine evoked an impaired catalysis in both mutants, the effects observed for mutant C49A were more severe: multiple conformational changes, caused by the loss of two hydrogen bonds, impeded proper substrate binding and thus the transfer of phosphate upon catalysis.

PubMed: 35998635
DOI: 10.1016/j.str.2022.08.001

実験手法

X-RAY DIFFRACTION (1.9 Å)