7R5Q

Escherichia coli type II Asparaginase N24S mutant in complex with GLU

7R5Q の概要

• エントリーDOI: 10.2210/pdb7r5q/pdb
• 関連するPDBエントリー: 5MQ5 7R57
• 分子名称: L-asparaginase 2, GLUTAMIC ACID (3 entities in total)
• 機能のキーワード: 3.5.1.1, asparaginase, ecaii, hydrolase, antitumor protein
• 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: 142303.16

構造登録者

Maggi, M.,Scotti, C. (登録日: 2022-02-11, 公開日: 2022-09-07, 最終更新日: 2024-10-16)

主引用文献

Maggi, M.,Scotti, C.
Structural Aspects of E. coli Type II Asparaginase in Complex with Its Secondary Product L-Glutamate.
Int J Mol Sci, 23:-, 2022

PubMed Abstract: Bacterial L-asparaginases are amidohydrolases (EC 3.5.1.1) capable of deaminating L-asparagine and, with reduced efficiency, L-glutamine. Interest in the study of L-asparaginases is driven by their use as biodrugs for the treatment of acute lymphoblastic leukemia. Here, we report for the first time the description of the molecular structure of type II asparaginase from in complex with its secondary product, L-glutamate. To obtain high-quality crystals, we took advantage of the N24S variant, which has structural and functional features similar to the wild-type enzyme, but improved stability, and which yields more ordered crystals. Analysis of the structure of the N24S-L-glutamate complex (N24S-GLU) and comparison with its apo and L-aspartate-bound form confirmed that the enzyme-reduced catalytic efficiency in the presence of L-glutamine is due to L-glutamine misfitting into the enzyme-binding pocket, which causes a local change in the catalytic center geometry. Moreover, a tight interaction between the two protomers that form the enzyme active site limits the capability of L-glutamine to fit into (and to exit from) the binding pocket of L-asparaginase, explaining why the enzyme has lower glutaminolytic activity compared to other enzymes of the same family, in particular the one.

PubMed: 35682622
DOI: 10.3390/ijms23115942

実験手法

X-RAY DIFFRACTION (1.9 Å)