Inhibition Profiling of Bestatin Against the Aminopeptidase B: in silico and in vitro Approach
Pushpa Bogra, Adarsh Kumar Shukla, Sanjeev Panwar, Ashwani Kumar, Jasbir Singh, Hari Singh
Abstract
Abstract Inhibitors of aminopeptidase B are potential drugs for the treatment of tumor angiogenesis, invasion and metastasis. Immunomodifier bestatin is used as an anticancer compound in many countries; its effect on aminopeptidase B activity was also analyzed. Molecular modeling, molecular docking and further biological evaluation were performed to uncover role of bestatin as an inhibitor of aminopeptidase B. The network profiling of bestatin has suggested that the amiopeptidase B is the potential target of it. After retrieval of sequence of aminopeptidase B of goat (accession no: XP_017916365.1), it was modeled for three-dimensional structure through Swiss Model and assigned as rigid molecule in protein-ligand docking used for AutoDock Vina. Molecular docking study predicted that the bestatin showed the high inhibitory effect against the aminopeptidase B with the minimum binding affinity (–8.4 kcal/mol). The purified aminopeptidase B from goat brain retained its activity in native 10% PAGE using Arg-βNA as substrate. The enzyme was activated by 150 mM NaCl and inhibited by EDTA. The EDTA inhibition was reversed by the addition of metal ions. Bestatin inhibited the enzyme competitively with the Ki value of 65 μM.