6UOH

Asparaginase II from Escherichia coli

6UOH の概要

• エントリーDOI: 10.2210/pdb6uoh/pdb
• 分子名称: L-asparaginase 2, ASPARTIC ACID (3 entities in total)
• 機能のキーワード: asparaginase, cancer, acute lymphoblastic leukemia, hydrolase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69519.74

構造登録者

Araujo, T.S.,Almeida, M.S.,Lima, L.M.T.R. (登録日: 2019-10-14, 公開日: 2020-10-21, 最終更新日: 2024-11-13)

主引用文献

de Araujo, T.S.,Scapin, S.M.N.,de Andrade, W.,Fasciotti, M.,de Magalhaes, M.T.Q.,Almeida, M.S.,Lima, L.M.T.R.
Biophysical characterization of two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2.
Biophys.Chem., 271:106554-106554, 2021

PubMed Abstract: The hydrolysis of asparagine and glutamine by L-asparaginase has been used to treat acute lymphoblastic leukemia for over four decades. Each L-asparaginase monomer has a long loop that closes over the active site upon substrate binding, acting as a lid. Here we present a comparative study of two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2 (EcA2), performed by a comprehensive array of biophysical and biochemical approaches. We report the oligomeric landscape and conformational and dynamic plasticity of E. coli type 2 L-asparaginase present in two different formulations, and its relationship with L-aspartic acid, which is present in Aginasa, but not in Leuginase. The L-Asp present in Aginasa formulation was found to provide to EcA2 a resistance to in vitro proteolysis. EcA2 shows a composition of monomers and oligomers up to tetramers, which is mostly not altered in the presence of L-Asp. Ion-mobility spectrometry-mass spectrometry reveals two conformers for the monomeric EcA2, and that monomeric species has sufficient capacity for selective binding to L-Asp and L-Glu. The N-terminal loop of the EcA2 present in Leuginase, which is part of the active site is disordered, but it gets ordered in the presence of L-Asp, while L-Glu only does so to a limited extent. These data provide new insights on the mechanistic of ligand recognition by EcA2, and the impact of formulation in its conformational diversity landscape.

PubMed: 33607531
DOI: 10.1016/j.bpc.2021.106554

実験手法

X-RAY DIFFRACTION (2.1 Å)