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Inhibition constant and stability of tripeptide inhibitors of gut trypsin-like enzyme of the soybean pest Anticarsia gemmatalis.
Arch Insect Biochem Physiol. 2022 Jun; 110(2):e21887.AI

Abstract

Insects overcome the action of natural protease inhibitors (PIs) due to evolutionary adaptations through endogenous proteolysis and reprogramming proteases. Insect adaptations complicate the formulation of IP-based crop protection products. However, small peptides designed based on the active site of enzymes have shown promising results that could change this scenario. GORE1 and GORE2 are designed tripeptides that reduce the survival of Anticarsia gemmatalis when ingested orally. In this article, the stability and ability of the peptides to bind trypsin-like enzymes of A. gemmatalis were evaluated by molecular dynamics (MD) simulations. The ability of the peptides to inhibit trypsin-like enzymes in vivo was compared with the SKTI protein by feeding A. gemmatalis larvae at different concentrations, followed by an inhibition persistence assay. During the MD simulation of enzyme-ligand complexes, both peptides showed a small variation of root-mean-square deviation and root-mean-square fluctuation, suggesting that these molecules reach equilibrium when forming a complex with the trypsin-like enzyme. Furthermore, both peptides form hydrogen bonds with substrate recognition sites of A. gemmatalis trypsin-like enzyme, with GORE2 having more interactions than GORE1. Larvae of A. gemmatalis exposed to the peptides and SKTI showed a similar reduction in proteolytic activity, but the persistence of inhibition of trypsin-like enzyme was longer in peptide-fed insects. Despite their size, the peptides exhibit important active and substrate binding site interactions, stability during complex formation, and steadiness effects in vivo. The results provide fundamental information for the development of mimetic molecules and help in decision-making for the selection of delivery methods for larger-scale experiments regarding similar molecules.

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Authors+Show Affiliations

de Almeida Barros R
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil.
Meriño-Cabrera Y
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil.
Severiche Castro JG
Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil. Departamento de Física, Universidad de Sucre, Sincelejo, Sucre, Colombia.
Rodrigues da Silva Júnior N
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil.
Schultz H
Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil. Departamento de Entomologia, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil.
de Andrade RJ
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil.
Aguilar de Oliveira JV
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil.
de Oliveira Ramos HJ
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil.
de Almeida Oliveira MG
Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil. Laboratory of Enzymology and Biochemistry of Proteins and Peptides, Instituto de Biotecnologia Aplicada à Agropecuária, BIOAGRO-UFV, Viçosa, Minas Gerais, Brazil.

MeSH

AnimalsFabaceaeLarvaMothsPeptidesSoybeansTrypsin

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35315942

Citation

de Almeida Barros, Rafael, et al. "Inhibition Constant and Stability of Tripeptide Inhibitors of Gut Trypsin-like Enzyme of the Soybean Pest Anticarsia Gemmatalis." Archives of Insect Biochemistry and Physiology, vol. 110, no. 2, 2022, pp. e21887.
de Almeida Barros R, Meriño-Cabrera Y, Severiche Castro JG, et al. Inhibition constant and stability of tripeptide inhibitors of gut trypsin-like enzyme of the soybean pest Anticarsia gemmatalis. Arch Insect Biochem Physiol. 2022;110(2):e21887.
de Almeida Barros, R., Meriño-Cabrera, Y., Severiche Castro, J. G., Rodrigues da Silva Júnior, N., Schultz, H., de Andrade, R. J., Aguilar de Oliveira, J. V., de Oliveira Ramos, H. J., & de Almeida Oliveira, M. G. (2022). Inhibition constant and stability of tripeptide inhibitors of gut trypsin-like enzyme of the soybean pest Anticarsia gemmatalis. Archives of Insect Biochemistry and Physiology, 110(2), e21887. https://doi.org/10.1002/arch.21887
de Almeida Barros R, et al. Inhibition Constant and Stability of Tripeptide Inhibitors of Gut Trypsin-like Enzyme of the Soybean Pest Anticarsia Gemmatalis. Arch Insect Biochem Physiol. 2022;110(2):e21887. PubMed PMID: 35315942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition constant and stability of tripeptide inhibitors of gut trypsin-like enzyme of the soybean pest Anticarsia gemmatalis. AU - de Almeida Barros,Rafael, AU - Meriño-Cabrera,Yaremis, AU - Severiche Castro,José G, AU - Rodrigues da Silva Júnior,Neilier, AU - Schultz,Halina, AU - de Andrade,Rafael J, AU - Aguilar de Oliveira,João V, AU - de Oliveira Ramos,Humberto J, AU - de Almeida Oliveira,Maria G, Y1 - 2022/03/22/ PY - 2022/02/08/revised PY - 2022/01/06/received PY - 2022/03/08/accepted PY - 2022/3/23/pubmed PY - 2022/5/18/medline PY - 2022/3/22/entrez KW - NAMD KW - inhibition persistence KW - larvae KW - pest control KW - total proteases SP - e21887 EP - e21887 JF - Archives of insect biochemistry and physiology JO - Arch Insect Biochem Physiol VL - 110 IS - 2 N2 - Insects overcome the action of natural protease inhibitors (PIs) due to evolutionary adaptations through endogenous proteolysis and reprogramming proteases. Insect adaptations complicate the formulation of IP-based crop protection products. However, small peptides designed based on the active site of enzymes have shown promising results that could change this scenario. GORE1 and GORE2 are designed tripeptides that reduce the survival of Anticarsia gemmatalis when ingested orally. In this article, the stability and ability of the peptides to bind trypsin-like enzymes of A. gemmatalis were evaluated by molecular dynamics (MD) simulations. The ability of the peptides to inhibit trypsin-like enzymes in vivo was compared with the SKTI protein by feeding A. gemmatalis larvae at different concentrations, followed by an inhibition persistence assay. During the MD simulation of enzyme-ligand complexes, both peptides showed a small variation of root-mean-square deviation and root-mean-square fluctuation, suggesting that these molecules reach equilibrium when forming a complex with the trypsin-like enzyme. Furthermore, both peptides form hydrogen bonds with substrate recognition sites of A. gemmatalis trypsin-like enzyme, with GORE2 having more interactions than GORE1. Larvae of A. gemmatalis exposed to the peptides and SKTI showed a similar reduction in proteolytic activity, but the persistence of inhibition of trypsin-like enzyme was longer in peptide-fed insects. Despite their size, the peptides exhibit important active and substrate binding site interactions, stability during complex formation, and steadiness effects in vivo. The results provide fundamental information for the development of mimetic molecules and help in decision-making for the selection of delivery methods for larger-scale experiments regarding similar molecules. SN - 1520-6327 UR - https://www.unboundmedicine.com/medline/citation/35315942/Inhibition_constant_and_stability_of_tripeptide_inhibitors_of_gut_trypsin_like_enzyme_of_the_soybean_pest_Anticarsia_gemmatalis_ DB - PRIME DP - Unbound Medicine ER -