A Structural In Silico Analysis of the Immunogenicity of L-Asparaginase from Penicillium cerradense

• Published in: International journal of molecular sciences Vol. 25; no. 9; p. 4788
• Main Authors: Andrade, Kellen Cruvinel Rodrigues, Homem-de-Mello, Mauricio, Motta, Julia Almeida, Borges, Marina Guimarães, de Abreu, Joel Antônio Cordeiro, de Souza, Paula Monteiro, Pessoa, Adalberto, Pappas, Jr, Georgios J, de Oliveira Magalhães, Pérola
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-05-2024
• Subjects: ALL; Amino Acid Sequence; Amino acids; Asparaginase - chemistry; Asparaginase - immunology; Asparaginase - metabolism; Aspergillus - enzymology; Aspergillus - immunology; Catalysis; Chemotherapy; Computer Simulation; Dickeya chrysanthemi - enzymology; Dickeya chrysanthemi - immunology; E coli; Enzymes; Epitopes, B-Lymphocyte - chemistry; Epitopes, B-Lymphocyte - immunology; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Escherichia coli - genetics; Fungal Proteins - chemistry; Fungal Proteins - immunology; Fungal Proteins - metabolism; Humans; immunogenicity; L-asparaginase; Microorganisms; Models, Molecular; Penicillium - enzymology; Penicillium - immunology; Penicillium cerradense; Phylogenetics; Polyethylene glycol; Protein synthesis; Proteins; Toxicity; Yeast; Penicillium cerradense; ALL; L-asparaginase; immunogenicity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25094788

L-asparaginase is an essential drug used to treat acute lymphoid leukemia (ALL), a cancer of high prevalence in children. Several adverse reactions associated with L-asparaginase have been observed, mainly caused by immunogenicity and allergenicity. Some strategies have been adopted, such as searching for new microorganisms that produce the enzyme and applying protein engineering. Therefore, this work aimed to elucidate the molecular structure and predict the immunogenic profile of L-asparaginase from
, recently revealed as a new fungus of the genus
and producer of the enzyme, as a motivation to search for alternatives to bacterial L-asparaginase. In the evolutionary relationship, L-asparaginase from
closely matches
species. Using in silico tools, we characterized the enzyme as a protein fragment of 378 amino acids (39 kDa), including a signal peptide containing 17 amino acids, and the isoelectric point at 5.13. The oligomeric state was predicted to be a homotetramer. Also, this L-asparaginase presented a similar immunogenicity response (T- and B-cell epitopes) compared to
and
enzymes. These results suggest a potentially useful L-asparaginase, with insights that can drive strategies to improve enzyme production.