7L21

Pyruvate Kinase M2 mutant-N70D

7L21 の概要

• エントリーDOI: 10.2210/pdb7l21/pdb
• 分子名称: Pyruvate kinase PKM, OXALATE ION, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: glycolysis, allosteric regulation, kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 243027.14

構造登録者

Nandi, S.,Dey, M. (登録日: 2020-12-16, 公開日: 2021-12-22, 最終更新日: 2023-10-25)

主引用文献

Nandi, S.,Dey, M.
Identification of residues involved in allosteric signal transmission from amino acid binding site of pyruvate kinase muscle isoform 2.
Plos One, 18:e0282508-e0282508, 2023

PubMed Abstract: PKM2 is a rate-limiting enzyme in the glycolytic process and is involved in regulating tumor proliferation. Several amino acids (AAs) such as Asn, Asp, Val, and Cys have been shown to bind to the AA binding pocket of PKM2 and modulate its oligomeric state, substrate binding affinity, and activity. Although previous studies have attributed that the main chain and side chain of bound AAs are responsible for initiating signal to regulate PKM2, the signal transduction pathway remains elusive. To identify the residues involved in signal transfer process, N70 and N75 located at two ends of a β strand connecting the active site and AA binding pocket were altered. Biochemical studies of these variants with various AA ligands (Asn, Asp, Val, and Cys), illustrate that N70 and N75, along with β1 connecting these residues are part of the signal transduction pathway between the AA binding pocket and the active site. The results demonstrate that mutation of N70 to D prevents the transfer of the inhibitory signal mediated by Val and Cys, whereas N75 to L alteration blocks the activating signal initiated by Asn and Asp. Taken together, this study confirms that N70 is one of the residues responsible for transmitting the inhibitory signal and N75 is involved in the activation signal flow.

PubMed: 36897854
DOI: 10.1371/journal.pone.0282508

実験手法

X-RAY DIFFRACTION (2.29 Å)