Báo cáo khoa học: Human mesotrypsin exhibits restricted S1¢ subsite specificity with a strong preference for small polar side chains

Human Mesotrypsin Exhibits Restricted S1′ Subsite Specificity with a Strong Preference for Small Polar Side Chains

Authors: Edit Szepessy and Miklós Sahin-Tóth

Field: Molecular and Cell Biology, Biochemistry

Document Content: This research investigates the substrate specificity of human mesotrypsin, a protease isoform known for its resistance to typical trypsin inhibitors. The study reveals that mesotrypsin exhibits a highly restricted specificity, particularly at the S1′ subsite, with a strong preference for small, polar amino acid side chains. This specificity explains mesotrypsin’s inability to activate pancreatic zymogens, a previously observed characteristic. The findings indicate that mesotrypsin is not a universally defective protease but rather one with a precisely defined substrate preference. Furthermore, the research demonstrates that the Pittsburgh variant of α₁-antitrypsin (α₁AT Pittsburgh) can effectively inhibit mesotrypsin, suggesting a potential therapeutic strategy by leveraging the serpin mechanism.

Detailed Table of Contents:

• Keywords
• Correspondence
• Abstract
• Introduction
• Results
• Discussion
• Experimental Procedures
• Nomenclature
• Acknowledgements
• References