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==Overview==

The type II transmembrane multidomain serine proteinase MT-SP1/matriptase, is highly expressed in many human cancer-derived cell lines and has been, implicated in extracellular matrix re-modeling, tumor growth, and, metastasis. We have expressed the catalytic domain of MT-SP1 and solved, the crystal structures of complexes with benzamidine at 1.3 A and bovine, pancreatic trypsin inhibitor at 2.9 A. MT-SP1 exhibits a trypsin-like, serine proteinase fold, featuring a unique nine-residue 60-insertion loop, that influences interactions with protein substrates. The structure, discloses a trypsin-like S1 pocket, a small hydrophobic S2 subsite, and an, open negatively charged S4 cavity that favors the binding of basic P3/P4, residues. A complementary charge pattern on the surface opposite the, active site cleft suggests a distinct docking of the preceding low density, lipoprotein receptor class A domain. The benzamidine crystals possess a, freely accessible active site and are hence well suited for soaking small, molecules, facilitating the improvement of inhibitors. The crystal, structure of the MT-SP1 complex with bovine pancreatic trypsin inhibitor, serves as a model for hepatocyte growth factor activator inhibitor 1, the, physiological inhibitor of MT-SP1, and suggests determinants for the, substrate specificity.

==About this Structure==

[[Category: serine proteinase]]