1eax
From Proteopedia
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[[Image:1eax.gif|left|200px]] | [[Image:1eax.gif|left|200px]] | ||
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'''CRYSTAL STRUCTURE OF MTSP1 (MATRIPTASE)''' | '''CRYSTAL STRUCTURE OF MTSP1 (MATRIPTASE)''' | ||
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[[Category: Bode, W.]] | [[Category: Bode, W.]] | ||
[[Category: Friedrich, R.]] | [[Category: Friedrich, R.]] | ||
| - | [[Category: | + | [[Category: Matrix degradation]] |
| - | [[Category: | + | [[Category: Serine proteinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:53:07 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:53, 2 May 2008
CRYSTAL STRUCTURE OF MTSP1 (MATRIPTASE)
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
1EAX is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Catalytic domain structures of MT-SP1/matriptase, a matrix-degrading transmembrane serine proteinase., Friedrich R, Fuentes-Prior P, Ong E, Coombs G, Hunter M, Oehler R, Pierson D, Gonzalez R, Huber R, Bode W, Madison EL, J Biol Chem. 2002 Jan 18;277(3):2160-8. Epub 2001 Nov 5. PMID:11696548 Page seeded by OCA on Fri May 2 14:53:07 2008
