Structural and functional diversity of asparaginases: Overview and recommendations for a revised nomenclature

Author(s)

da Silva, Leonardo Schultz ; Doonan, Liam B. ; Pessoa, Adalberto, Jr. ; de Oliveira, Marcos Antonio ; Long, Paul F.

• Document type: Journal article
• Source: Biotechnology and Applied Biochemistry; v. 69, n. 2, p. 11-pg., 2021-03-19.

Abstract

Asparaginases (ASNases) are a large and structurally diverse group of enzymes ubiquitous amongst archaea, bacteria and eukaryotes, that catalyze hydrolysis of asparagine to aspartate and ammonia. Bacterial ASNases are important biopharmaceuticals for the treatment of acute lymphoblastic leukemia, although some patients experience adverse allergic side effects during treatment with these protein therapeutics. ASNases are currently divided into three families: plant-type ASNases, Rhizobium etli-type ASNases and bacterial-type ASNases. This system is outdated as both bacterial-type and plant-type families also include archaeal, bacterial and eukaryotic enzymes, each with their own distinct characteristics. Herein, phylogenetic studies allied to tertiary structural analyses are described with the aim of proposing a revised and more robust classification system that considers the biochemical diversity of ASNases. Accordingly, based on distinct peptide domains, phylogenetic data, structural analysis and functional characteristics, we recommend that ASNases now be divided into three new distinct classes containing subgroups according to structural and functional aspects. Using this new classification scheme, 25 ASNases were identified as candidates for future new lead discovery. (AU)

• FAPESP's process: 18/04685-1 - Biological diversity of ASNAses: evaluation of enzyme evolution and determination of the crystallographic structure of the ASNaseM
• Grantee: Leonardo Schultz da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 13/08617-7 - Production of extracellular L-asparaginase: from bioprospecting to the engineering of an antileukemic biopharmaceutical
• Grantee: Adalberto Pessoa Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/19942-7 - Search for inhibitors of the peroxirredoxin system from pathogens and humans
• Grantee: Marcos Antonio de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/22039-9 - Functional and structural characterization and rational modification of ASPaseM: a new pharmaceutical for the acute lymphoblastic leukemia treatment?
• Grantee: Leonardo Schultz da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)