Crystallization and preliminary crystallographic analysis of L-asparaginase from Erwinia carotovora

Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
Linnea E K WikmanAnastassios C Papageorgiou

Abstract

Bacterial L-asparaginases have been used as therapeutic agents in the treatment of acute childhood lymphoblastic leukaemia for over 30 y. However, their use is limited owing to the glutaminase activity of the administered enzymes, which results in serious side effects. In contrast, L-asparaginase from Erwinia carotovora exhibits low glutaminase activity at physiological concentrations of L-asparagine and L-glutamine in the blood. Recombinant Er. carotovora L-asparaginase was crystallized in the presence of L-glutamate by the hanging-drop vapour-diffusion method using 10 mg ml(-1) purified enzyme, 16-18%(w/v) PEG 3350 and 0.2 M NaF. X-ray diffraction data were collected to 2.6 A at 293 K using an in-house rotating-anode generator. The crystals belong to the monoclinic P2(1) space group, with unit-cell parameters a = 78.0, b = 112.3, c = 78.7 A, beta = 101.9 degrees and a homotetramer in the crystallographic asymmetric unit. A molecular-replacement solution has been found and refinement is currently in progress. The crystal structure may provide leads towards protein-engineering efforts aimed at safer asparaginase administration in leukaemia treatment.

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Citations

Jul 24, 2008·The FEBS Journal·Anastassios C PapageorgiouJulya Krasotkina
Jul 29, 2015·Biomedit︠s︡inskai︠a︡ khimii︠a︡·N N SokolovA I Archakov
Feb 23, 2007·The Biochemical Journal·Georgia A KotziaNikolaos E Labrou
Nov 2, 2011·Journal of Pediatric Hematology/oncology·Vassilios I Avramis
Nov 18, 2018·Molecular Biology Reports·Marcele FaretTatiana de Arruda Campos Brasil de Souza

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