8ECE

E. coli L-asparaginase II mutant (V27T) in complex with L-Glu

8ECE の概要

• エントリーDOI: 10.2210/pdb8ece/pdb
• 分子名称: L-asparaginase 2, GLUTAMIC ACID, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: hydrolase, hydrolysis of l-asparagine
• 由来する生物種: Escherichia coli K-12
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 143714.61

構造登録者

Strzelczyk, P.,Wlodawer, A.,Lubkowski, J. (登録日: 2022-09-01, 公開日: 2022-11-16, 最終更新日: 2024-11-06)

主引用文献

Strzelczyk, P.,Zhang, D.,Wlodawer, A.,Lubkowski, J.
The E. coli L-asparaginase V27T mutant: structural and functional characterization and comparison with theoretical predictions.
Febs Lett., 596:3060-3068, 2022

PubMed Abstract: Bacterial L-asparaginases have been used for over 40 years as anticancer drugs. Ardalan et al. (Medical Hypotheses 112, 7-17, 2018) proposed that the V27T mutant of Escherichia coli type II L-asparaginase, EcAII(V27T), should display altered biophysical and catalytic properties compared to the wild-type enzyme, EcAII(wt), rendering it more favourable as a pharmaceutical. They postulated that EcAII(V27T) would exhibit reduced glutaminolytic activity and be more stable compared to EcAII(wt). Their postulates, however, were purely theoretical. Here, we characterized experimentally selected properties of EcAII(V27T). We found asparaginolytic activity of this mutant unchanged, whereas its glutaminolytic activity was fourfold lower compared with EcAII(wt). We did not observe significant differences in stabilities of EcAII(wt) and EcAII(V27T). Crystal structures of the complexes with L-Asp and L-Glu showed considerable differences in binding modes of both substrates.

PubMed: 36310372
DOI: 10.1002/1873-3468.14526

実験手法

X-RAY DIFFRACTION (1.86 Å)