A Novel trypsin-like enzyme in breast cancer

Structure of the complex of leech-derived tryptase inhibitor (LDTI) with trypsin and modeling of the LDTI–tryptase system

“…The insertion The solvent accessible surface area [42] after residue 174 would also explain the inability of the Kunitz-type erythrina trypsin inhibitor (ETI), whose uncomplexed structure has been solved [29], to inhibit tryptase. Although ETI is from a different inhibitor family, structural alignment based solely on the binding loop (residues 61-66) gives an rms deviation of Cα positions of 0.52 Å with the corresponding residues of LDTI (6)(7)(8)(9)(10)(11). As aligned, the 174 loop of tryptase would cause steric clashes with loops 111-115 and 70-74 of ETI.…”

“…Mast cell tryptase has also been implicated in tumorgenesis and angiogenesis due to its potential to activate enzymes involved in matrix degradation, for example prourokinase and the matrix metalloproteinase prostromelysin [4,5]. Recently, a tryptase-like enzyme activity has been detected in several breast cancer cell lines [6]. Tryptase-like enzymes have also been described as taking part in the activation and internalization of pathogenic viruses such as influenza virus, Sendai virus and human immunodeficiency virus (HIV) [7,8].…”