1EAX

Crystal structure of MTSP1 (matriptase)

1EAX の概要

• エントリーDOI: 10.2210/pdb1eax/pdb
• 関連するPDBエントリー: 1EAW
• 分子名称: SUPPRESSOR OF TUMORIGENICITY 14, SULFATE ION, BENZAMIDINE, ... (4 entities in total)
• 機能のキーワード: hydrolase, serine proteinase, matrix degradation
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Membrane ; Single-pass type II membrane protein : Q9Y5Y6
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26679.97

構造登録者

Friedrich, R.,Bode, W. (登録日: 2001-07-17, 公開日: 2002-01-28, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.3 Å)