Mutations in asparaginase II from E. coli and implications for inactivation and PEGylation

Article Biochemical Research Methods

The reproducible normality of the crystallographic B-factor

Natalia Goncalves Ramos et al.

Summary: This study evaluated the reproducibility of uncertainties in protein crystallography and found that empirical scaling/normalization can result in reproducible B-factors.

ANALYTICAL BIOCHEMISTRY (2022)

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Article Biotechnology & Applied Microbiology

Single-sequence protein structure prediction using a language model and deep learning

Ratul Chowdhury et al.

Summary: This article reports the development of an end-to-end differentiable recurrent geometric network (RGN) called RGN2 for predicting protein structure using the protein sequence. Compared to AlphaFold2 and RoseTTAFold, RGN2 performs better on orphan proteins and designed protein classes, while achieving a computational speedup of up to 10^6-fold. These findings demonstrate the practical and theoretical advantages of protein language models over multiple sequence alignments (MSAs) in protein structure prediction.

NATURE BIOTECHNOLOGY (2022)

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Review Oncology

Human L-asparaginase: Acquiring knowledge of its activation (Review)

Stephanie Bath De Morais et al.

Summary: L-asparaginase enzymes have been crucial in acute lymphoblastic leukemia therapy for over 40 years by depleting plasma L-asparagine essential for leukemia cell survival. While bacterial enzymes used in therapy have severe side-effects, efforts are focused on developing a therapeutic variant of human L-asparaginase to avoid these problems.

INTERNATIONAL JOURNAL OF ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

Biophysical characterization of two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2

Talita Stelling de Araujo et al.

Summary: The hydrolysis of asparagine and glutamine by L-asparaginase has been used in treating acute lymphoblastic leukemia for over four decades. A comparative study of two commercially available preparations of the drug containing Escherichia coli L-Asparaginase 2 (EcA2) showed that the presence of L-Asp in the Aginasa formulation provides resistance to in vitro proteolysis for EcA2. Additionally, the study revealed the oligomeric landscape and conformational diversity of EcA2, as well as insights into ligand recognition by the enzyme.

BIOPHYSICAL CHEMISTRY (2021)

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Article Oncology

Unsatisfactory quality of E. coli asparaginase biogenerics in India: Implications for clinical outcomes in acute lymphoblastic leukaemia

Jasmeet Sidhu et al.

Summary: This study evaluated seven biogeneric EcASNases marketed in India and found the presence of isoforms and impurities, resulting in low therapeutic activity and hypersensitivity reactions. Monitored studies are needed to determine the clinical suitability and appropriate dosing and schedule for these products. Access to high-quality asparaginases remains a therapeutic need in many parts of the world.

PEDIATRIC BLOOD & CANCER (2021)

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Letter Oncology