1EAX
Crystal structure of MTSP1 (matriptase)
Summary for 1EAX
| Entry DOI | 10.2210/pdb1eax/pdb |
| Related | 1EAW |
| Descriptor | SUPPRESSOR OF TUMORIGENICITY 14, SULFATE ION, BENZAMIDINE, ... (4 entities in total) |
| Functional Keywords | hydrolase, serine proteinase, matrix degradation |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Membrane ; Single-pass type II membrane protein : Q9Y5Y6 |
| Total number of polymer chains | 1 |
| Total formula weight | 26679.97 |
| Authors | Friedrich, R.,Bode, W. (deposition date: 2001-07-17, release date: 2002-01-28, Last modification date: 2024-10-09) |
| Primary citation | Friedrich, R.,Fuentes-Prior, P.,Ong, E.,Coombs, G.,Hunter, M.,Oehler, R.,Pierson, D.,Gonzalez, R.,Huber, R.,Bode, W.,Madison, E.L. Catalytic Domain Structures of Mt-Sp1/Matriptase, a Matrix-Degrading Transmembrane Serine Proteinase. J.Biol.Chem., 277:2160-, 2002 Cited by PubMed Abstract: 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. PubMed: 11696548DOI: 10.1074/JBC.M109830200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.3 Å) |
Structure validation
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