Leech, potato, and tomato carboxypeptidase inhibitors against Anopheles stephensi carboxypeptidase B1 and B2

• Published in: Archives of biochemistry and biophysics Vol. 759; p. 110086
• Main Authors: Rismani, Elham, Mafakher, Ladan, Asgari, Majid, Raz, Abbasali
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2024
• Subjects: Animals; Anopheles - enzymology; Anopheles stephensi; Carboxypeptidase B; Carboxypeptidase B - antagonists & inhibitors; Carboxypeptidase B - chemistry; Carboxypeptidase B - metabolism; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Inhibitors; Insect Proteins - antagonists & inhibitors; Insect Proteins - chemistry; Insect Proteins - genetics; Insect Proteins - metabolism; Malaria; Malaria transmission blocking; Molecular Docking Simulation; Molecular Dynamics Simulation; Solanum lycopersicum - enzymology; Solanum tuberosum; Malaria transmission blocking; Anopheles stephensi; Inhibitors; Carboxypeptidase B; Malaria
• ISSN: 0003-9861; 1096-0384; 1096-0384
• DOI: 10.1016/j.abb.2024.110086

Carboxypeptidase B (CPB) in Anopheles spp. breaks down blood and releases free amino acids, which promote Plasmodium sexual development in the mosquito midgut. Our goal was to computationally assess the inhibitory effectiveness of carboxypeptidase inhibitors obtained from tomato, potato (CPiSt), and leech against the Anopheles stephensi CPBAs1 and CPBAs2 enzymes. The tertiary structures of CPB inhibitors were predicted and their interaction mode with CPBAs1 and CPBAs2 were examined using molecular docking. Next, this data was compared with four licensed medications that are known to reduce the Anopheles’ CPB activity. Molecular dynamics simulations were used to evaluate the stability of complexes containing CPiSt and its mutant form. Both CPiSt and its mutant form showed promise as possible candidates for further evaluations in the paratransgenesis technique for malaria control, based on the similar bindings of CPiSt and CPiSt-Mut to the active sites of CPBAs1 and CPBAs2, as well as their binding affinity in comparison to the drugs. [Display omitted] •Computationally assess the inhibitory capability of carboxypeptidase (CPB) inhibitors.•Assess inhibitors from tomato, potato, and leech against An. stephensi's CPB.•Physicochemical properties and potential aggregation hotspots of the inhibitors.•Potato inhibitor and its mutant form effectively interacted with CPB.•Potato inhibitor and its mutant form as candidates for paratransgenesis.