5F52

Erwinia chrysanthemi L-asparaginase + Aspartic acid

5F52 の概要

• エントリーDOI: 10.2210/pdb5f52/pdb
• 関連するPDBエントリー: 5F65 5F8D
• 分子名称: L-asparaginase, ASPARTIC ACID, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• 機能のキーワード: l-asparaginase, erwinia chrysanthemum, aspartic acid, hydrolase
• 由来する生物種: Dickeya chrysanthemi (Pectobacterium chrysanthemi, Erwinia chrysanthemi)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 142236.12

構造登録者

Nguyen, H.A.,Lavie, A. (登録日: 2015-12-04, 公開日: 2016-04-06, 最終更新日: 2023-09-27)

主引用文献

Nguyen, H.A.,Su, Y.,Lavie, A.
Structural Insight into Substrate Selectivity of Erwinia chrysanthemi l-Asparaginase.
Biochemistry, 55:1246-1253, 2016

PubMed Abstract: l-Asparaginases of bacterial origin are a mainstay of acute lymphoblastic leukemia treatment. The mechanism of action of these enzyme drugs is associated with their capacity to deplete the amino acid l-asparagine from the blood. However, clinical use of bacterial l-asparaginases is complicated by their dual l-asparaginase and l-glutaminase activities. The latter, even though representing only ∼10% of the overall activity, is partially responsible for the observed toxic side effects. Hence, l-asparaginases devoid of l-glutaminase activity hold potential as safer drugs. Understanding the key determinants of l-asparaginase substrate specificity is a prerequisite step toward the development of enzyme variants with reduced toxicity. Here we present crystal structures of the Erwinia chrysanthemi l-asparaginase in complex with l-aspartic acid and with l-glutamic acid. These structures reveal two enzyme conformations-open and closed-corresponding to the inactive and active states, respectively. The binding of ligands induces the positioning of the catalytic Thr15 into its active conformation, which in turn allows for the ordering and closure of the flexible N-terminal loop. Notably, l-aspartic acid is more efficient than l-glutamic acid in inducing the active positioning of Thr15. Structural elements explaining the preference of the enzyme for l-asparagine over l-glutamine are discussed with guidance to the future development of more specific l-asparaginases.

PubMed: 26855287
DOI: 10.1021/acs.biochem.5b01351

実験手法

X-RAY DIFFRACTION (1.63 Å)