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Publication Abstract from PubMed

Serine proteases are involved in various ailments, including pancreatitis, and colon cancer. Based on substrate recognition serine proteases are classified into different groups. Trypsin and trypsin-like serine proteases are among most studied group of serine proteases. Trypsin is among the chief hydrolysing enzyme involved in the pathogenesis of pancreatitis. Its inhibition can help to manage the disease. Herein, we investigated the trypsin inhibitory effect of some arginine-based small molecules, through in vitro, in silico, and crystallographic methods. Compounds 1-3 were evaluated against bovine pancreatic trypsin (BPT). Compound 1 was found to be active against trypsin with IC(50) value of 247.98 +/- 2.44 muM. Molecular docking studies were used to investigate the binding energy and binding conformation of inhibitor. All three compounds were subjected to crystallisation with trypsin. Compounds 1-2 were successfully crystallised with BPT The crystal structures of trypsin in complexed with compounds 1, and 2 were determined at 2.30 and 2.50 A resolution, respectively. Both molecules showed their binding affinity with the active site residues of trypsin. This study will provide insight into the binding mechanism of E-64 and arginine and might be useful in designing effective inhibitors of serine proteases.

In vitro, in silico and crystallographic-based identification of serine protease inhibitors.,Akbar Z, Ahmad MS Nat Prod Res. 2024 Nov 9:1-7. doi: 10.1080/14786419.2024.2425793. PMID:39520718^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.