%0 Journal Article
%T Structure of catalytic domain of Matriptase in complex with Sunflower trypsin inhibitor-1
%A Cai Yuan
%A Liqing Chen
%A Edward J Meehan
%A Norelle Daly
%A David J Craik
%A Mingdong Huang
%A Jacky C Ngo
%J BMC Structural Biology
%D 2011
%I BioMed Central
%R 10.1186/1472-6807-11-30
%X We have engineered and produced recombinant proteins of the matriptase protease domain, and have determined the crystal structures of the protease:SFTI-1 complex at 2.0 £¿ as well as the protease:benzamidine complex at 1.2 £¿. These structures elaborate the structural basis of substrate selectivity of matriptase, and show that the matriptase S1 substrate specificity pocket is larger enough to allow movement of benzamidine inside the S1 pocket. Our study also reveals that SFTI-1 binds to matriptase in a way similar to its binding to trypsin despite the significantly different isoelectric points of the two proteins (5.6 vs. 8.2).This work helps to define the structural basis of substrate specificity of matriptase and the interactions between the inhibitor and protease. The complex structure also provides a structural template for designing new SFTI-1 derivatives with better potency and selectivity against matriptase and other proteases.Matriptase is a type II transmembrane serine protease of the S1 trypsin-like family. Matriptase activity is down-regulated by its physiological inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1) [1-3]. Matriptase is expressed in most epithelial cells and plays essential roles in the establishment and maintenance of epithelial integrity. New evidence suggests that matriptase is also expressed on mast cells, peripheral blood monocytes and B cells, implicating matriptase in the physiological and pathologic functions of these cells [4-6]. Knock down studies in mice have shown that the protease is important in postnatal survival, epidermal barrier formation, hair follicle growth and thymichomeostasis [7]. At the same time, genetic studies using zebra fish and mice have indicated that the activity of matriptase is critical for tissue-integrity and function, and must be strictly controlled by HAI-1 [8-11].The catalytic domain of matriptase is tethered to the cell surface via its N-terminal signal anchor, linked by a sea urchin spe
%U http://www.biomedcentral.com/1472-6807/11/30