1EAW

Crystal structure of the MTSP1 (matriptase)-BPTI (aprotinin) complex

Summary for 1EAW

• Entry DOI: 10.2210/pdb1eaw/pdb
• Related: 1EAX
• Descriptor: SUPPRESSOR OF TUMORIGENICITY 14, PANCREATIC TRYPSIN INHIBITOR (3 entities in total)
• Functional Keywords: hydrolase/inhibitor, complex (serine protease inhibitor), serine proteinase, matrix degradation, inhibitor, glycoprote hydrolase, hydrolase-inhibitor complex
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Membrane ; Single-pass type II membrane protein : Q9Y5Y6; Secreted: P00974
• Total number of polymer chains: 4
• Total formula weight: 65982.65

Authors

Friedrich, R.,Bode, W. (deposition date: 2001-07-17, release date: 2002-01-28, Last modification date: 2024-11-13)

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

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: 11696548
DOI: 10.1074/JBC.M109830200

Experimental method

X-RAY DIFFRACTION (2.93 Å)