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7QY6

Structure of E.coli Class 2 L-asparaginase EcAIII, wild type (WT EcAIII)

これはPDB形式変換不可エントリーです。
7QY6 の概要
エントリーDOI10.2210/pdb7qy6/pdb
関連するPDBエントリー7QQ8 7QSF 7QTC 7QVR
分子名称Isoaspartyl peptidase, Beta-aspartyl-peptidase, SODIUM ION, ... (5 entities in total)
機能のキーワードl-asparaginase, mutation, hydrolase
由来する生物種Escherichia coli
詳細
タンパク質・核酸の鎖数4
化学式量合計67000.72
構造登録者
Loch, J.I.,Klonecka, A.,Kadziolka, K.,Bonarek, P.,Barciszewski, J.,Imiolczyk, B.,Brzezinski, K.,Jaskolski, M. (登録日: 2022-01-27, 公開日: 2022-07-13, 最終更新日: 2024-01-31)
主引用文献Loch, J.I.,Klonecka, A.,Kadziolka, K.,Bonarek, P.,Barciszewski, J.,Imiolczyk, B.,Brzezinski, K.,Gilski, M.,Jaskolski, M.
Structural and biophysical studies of new L-asparaginase variants: lessons from random mutagenesis of the prototypic Escherichia coli Ntn-amidohydrolase.
Acta Crystallogr D Struct Biol, 78:911-926, 2022
Cited by
PubMed Abstract: This work reports the results of random mutagenesis of the Escherichia coli class 2 L-asparaginase EcAIII belonging to the Ntn-hydrolase family. New variants of EcAIII were studied using structural, biophysical and bioinformatic methods. Activity tests revealed that the L-asparaginase activity is abolished in all analyzed mutants with the absence of Arg207, but some of them retained the ability to undergo the autoproteolytic maturation process. The results of spectroscopic studies and the determined crystal structures showed that the EcAIII fold is flexible enough to accept different types of mutations; however, these mutations may have a diverse impact on the thermal stability of the protein. The conclusions from the experiments are grouped into six lessons focused on (i) the adaptation of the EcAIII fold to new substitutions, (ii) the role of Arg207 in EcAIII activity, (iii) a network of residues necessary for autoprocessing, (iv) the complexity of the autoprocessing reaction, (v) the conformational changes observed in enzymatically inactive variants and (vi) the cooperativity of the EcAIII dimer subunits. Additionally, the structural requirements (pre-maturation checkpoints) that are necessary for the initiation of the autocleavage of Ntn-hydrolases have been classified. The findings reported in this work provide useful hints that should be considered before planning enzyme-engineering experiments aimed at the design of proteins for therapeutic applications. This is especially important for L-asparaginases that can be utilized in leukemia therapy, as alternative therapeutics are urgently needed to circumvent the severe side effects associated with the currently used enzymes.
PubMed: 35775990
DOI: 10.1107/S2059798322005691
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (1.65 Å)
構造検証レポート
Validation report summary of 7qy6
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件を2024-10-30に公開中

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